Neuropathy Update

June 25 – 28

Vienna, Austria

Neuropathy Update

Sl. No.

Content

Page No.

Diagnostic tests for small fiber neuropathy.

Why are some neuropathies painful and others not?

Symptomatic pharmacological and topical treatment of peripheral neuropathic pain

Immune-mediated small fiber neuropathy: classification, diagnosis and treatment

Does small fiber neuropathy contribute to chronic muscle pain in patients with myotonic dystrophy?

Vitamin B12 deficiency-related neurological manifestations: 5 years of experience in a Portuguese tertiary center

Peripheral neuropathy and MOG-IgG: a clinical and neuropathological retrospective study

Photobiomodulation therapy for the prevention of chemotherapyinduced peripheral neuropathy (NEUROLASER trial)

Cannabinoids for painful dystonia in corticobasal syndrome: a report of three patients.

Antibody Response after COVID-19 Vaccination in IVIg Dependent Immune Neuropathies: An Observational Study

The Spectrum of Bilateral Optic Neuropathy: a case series

Facial neuropathy secondary to cocaine use: an infrequent and refractory entity

Fiber neuropathy following SARSCOV-19 vaccination. A case series

Young-onset Parkinsonism and neuropathy in FIG4 gene mutations

Optic neuropathy secondary to Herpes Zoster virus

Peripheral neuropathy following COVID-19 mRNA vaccination – 2 Case Reports

Clinical and electrophysiological characteristics of COVID and post COVID polyneuropathies in adults and paediatrics

Peripheral neuropathy due to neuroborreliosis: Insensitivity for CXCL13 as early diagnostic marker

Peripheral neuropathy in myotonic dystrophy type 1 patients

The role of beta-NGF in the maintenance of chronic neuropathic pain in post-traumatic neuropathies and plexopathies

IVIg responsive neuropathy associated with the treatment of cutaneous T-cell lymphoma with Brentuximab

Patient Characteristics from the NEURO-TTRansform Study of Eplontersen in Transthyretin Amyloidosis Polyneuropathy

Bilateral optic neuropathy secondary to Vitamin B12 deficiency

Multiple cranial mononeuropathy secondary to adecarcinoma in a young patient

The great mimic: An elusive diagnosis for a multiple cranial polyneuropathy

Celiac disease and peripheral neuropathy: identifying pleiotropic SNPs among established genetic risk variants

Descriptive Analysis of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in the Northern Area of Tenerife

A case series on a rare diagnosis: Idiopathic Painful Nervus Intermedius Neuropathy

Electrodiagnosis of ulnar neuropathy at the elbow

Features of Chronic Inflammatory Demyelinating Polyneuropathy in different age groups at disease onset

1. Diagnostic tests for small fiber neuropathy.

Speaker: Jordi Serra

Polyneuropathies are clinically diverse. Small fiber neuropathy manifests in a variety of different diseases and often results in symptoms of burning pain, shooting pain, allodynia, and hyperesthesia. A small fiber neuropathy occurs when damage to the peripheral nerves predominantly or entirely affects the small myelinated (Aδ) fibers or unmyelinated C fibers. The sensory functions of these fibers include thermal perception and nociception. These fibers also are involved in a number of autonomic and enteric functions. The nerve conduction and SEP studies can only assess large myelinated fiber function (Amp + CV) and deficits. However, they cannot assess small myelinated and unmyelinated nerve fiber function and positive sensory phenomena.

Techniques (`reasonably’) available

1. Quantitative sensory testing

» It is a psychophysical test:

• ‘Physical’ because we apply an energy to the body, most often the skin.

• ‘Psycho’ because we obtain a conscious response

» Psychophysical measure of the perception threshold responses to non-painful and painful stimuli (mechanical, thermal).

» Normally the stimuli are controlled by an automated device.

» The patient signals when experiencing a pre-specified percept. 2. Skin biopsy / Determination of IENFD

» Can assess small unmyelinated fiber density.

» It has become a ‘gold standard’.

» Good specificity, rather poor sensitivity. 3. Laser evoked potentials & CHEPS

» They assess:

• Small myelinated and unmyelinated fiber function: yes

• Positive sensory phenomena: no

» Objective, noninvasive, physiological evaluation of small fibers.

» Possibility to document small-fiber sensory deficit

4. Pain-related intraepidermal electrically evoked potentials

» Objective, noninvasive, physiological evaluation of small fibers.

» No skin reactions as seen with laser or CHEPS.

» Possibility to document small-fiber sensory deficit.

» Unexpensive stimulating electrodes.

» Conventional electrophysiological amplifiers. 5. Corneal confocal microscopy

» CCM is another morphological technique to evaluate small nerve fibers.

» Non-invasive technique that allows in vivo quantification of corneal nerve fibers.

» Not only density, but also some morphological traits.

» Increasingly considered in SFN evaluation.

6. Microneurography

» for direct recording of sympathetic action potentials from unmyelinated postganglionic fibers in alert patients.

» allows a broader analysis of peripheral sympathetic outflow exploring additional muscle sympathetic nerve activity (MSNA).

» allows the measurement of sympathetic reflex latencies that can be used as a sympathetic velocity index since sympathetic latency is mainly due to conduction in postganglionic sympathetic fibers.

An Atypical Conclusion

Medical advancements often come with the appearance of new technologies.

2. Why are some neuropathies painful and others not?

(Speaker: Giuseppe Lauria, EAN 2022)

The reason behind why some neuropathies are painful and others not are because of unknown reason, some new hypotheses and some new candidate molecular biomarkers availability. In squid, nociceptors have coiled terminals embedded in the muscle layer rather than the skin which can explain why sharp poking or pinching stimuli produce optimal activation, and light, brushing stimuli are ineffective. These neurons are not activated by noxious heat but have mechanical thresholds in the same range (10 g) as nociceptors in mammals.

In sensitization from minor fin injury, dramatic decrease of mechanosensory and electrical thresholds and in spontaneous activity (SA) after crush, long-lasting SA in afferent neurons not only near the injury site but also on the other side of the body Fins are innervated separately and separated by the mantle, suggesting that CNS drives the spread of SA into the opposite fin.

Pain an d behavior

» Temporary blockade of nociceptor activity during injury provided the first demonstration of the adaptiveness of nociceptive sensitization.

» In squids, the response to tissue damage evolved as a survival tactic to measurably reduce predation risk.

» Injured squids fled from predators at a greater distance than non-injured ones, with 45% survival rate compared

with 80% of uninjured squids.

» However, when squid were anaesthetised during injury such that they did not experience the associated negative affective component, they did not show an enhanced flight and were more vulnerable to predation, with only 19% animals surviving.

» Thus, the cost of injury is 35% mortality, but if the experience of the injury is blocked via anaesthesia the mortality cost rises to 61%.

Nociception and Pain

» Pain does not just involve nociception but encompasses negative affective component leading to behavioural changes, which are species dependent.

» The advantage that action can be taken when damage occurs, consequent learning allows the minimizing of future damage and, where the pain is chronic, behaviour and physiology can be changed to ameliorate adverse effects.

In the case of diabetic neuropathy, most common neuropathy in Western countries, with expected rising prevalence. Major risk of ulcer and limb amputation and most commonly painless (70-80%).

Brain-based facilitation mechanism in painful diabetic neuropathy

» The descending pain modulatory system (DPMS) has key role in central sensitisation, hyperalgesia and allodynia, and its dysfunction correlates with clinical measures of pain.

» Hypothesis: altered connectivity between ventrolateral periacqueductal grey (vIPAG) and anterior cingulate cortex (ACC) could explain painful and painless DN differences.

Dynamic nature of connectivity

» Salience network: a suite of brain regions whose cortical hubs are the anterior cingulate (ACC) and frontoinsular (aINS) cortices. Also, nodes in the amygdala, hypothalamus, ventral striatum, thalamus, and brainstem nuclei. It coactivates in response to diverse experimental tasks and conditions, with a domain general function.

» In monkeys, homologous regions are interconnected with limbic, subcortical, and brainstem sites involved in autonomic processing and emotion. ACC and aINS coactivate in the context of diverse tasks and conditions, ranging from those designed to induce thirst, hunger, pain, bladder distention, embarrassment, and uncertainty to those eliciting amusement, compassion, tenderness, and humor.

» Default mode network (DMN): a baseline brain functioning widely distributed in the parietal, temporal and frontal cortex that is suspended during specific goal directed behaviours.

Dynamic nature of pain connectome

» Pain is dynamic in nature and fluctuations change with environment or in individual’s cognitive states.

» Chronic pain occurs due to a complex integration between activity in ascending nociceptive pathways and

descending modulation pathways, the latter influenced by top-down attentional controls.

» DMN, salience network, and connectivity with antinociceptive areas (PAG) are modulated when subjects attended to pain versus mind wandered from pain.

» Intrinsic attention to pain changes the functional connectivity between DMN and antinociceptive (PAG). The theory of constructed emotion

Dynamics of the DNM and salience networks form the computational core of a brain’s working model, to create multi-sensory representations of the world at various time scales, all in the service of allostasis. Unanticipated information (prediction error) would function as feedback for embodied simulations. Prediction errors might be pre-elaborated, influencing the processing of prediction errors before they even reach the brain. A new hypothesis that considers chronic pain and emotion as two sides of the same coin, rather than separate phenomena that influence one another.

Nav1.7 gene variants suggest evolutionary susceptibility to pain

» Neanderthals carried Nav1.7 substitutions (M932L, V991L, and D1908G) found in painful neuropathies.

» Full variants and the combination V991L with D1908G showed reduced channel inactivation in cell

electrophysiology assay.

» Peripheral nerves might be more sensitive to painful stimuli in Neanderthals than in modern humans.

p.Trp1538Arg variant in SCN9A impairs lacosamide’s analgesic affect

» p.Try1538Arg mutation abolish the effect of lacosamide on slow-inactivation and use-dependent inhibition of the channel at clinically-achievable concentrations.

» Unlike typical antiepileptic drugs (AEDs) such as carbamazepine, phenytoin, and lamotrigine, as well as local anesthetics (LAS), such as lidocaine and benzocaine, lacosamide enhances the voltage-dependence of slow inactivation but not steady-state fast inactivation, and increases use-dependent inhibition of sodium channels.

Summary

The approach to painful and non-painful is different, even if the patient has the same neuropathy.

3. Symptomatic pharmacological and topical treatment of peripheral neuropathic pain

(Speaker: Ralf Baron, EAN 2022)

Neuropathic pain is a pain that arises as a direct consequence of a lesion or disease affecting the somatosensory system: Peripheral nervous system and Central nervous system. Mechanisms of peripheral sensitization includes Na- channel expression and TRPV1 receptor expression. Pain attacks and burning with symptom attacks and mechanism includes Na-channels, peripheral sensitization and ectopic activity.

Na-Channels

» The mechanism include for Physiology are peripheral sensizization, ectopic activity and Molecular includes NaV 1.7 channel expression.

» The evidence includes entities-increased TGN, Agents-Carbamazepine, Oxcarbazepine, Dose range- Titration, CA: 600 – 1400 mg and others with Bothersome side effects.

Lidocain Topical

» Entities; PHN increase

» Agents: Lidocaine patch

» Dose range: 5%, 12 h on – 12 h off

» Add on therapy, few local side effects, no interactions

Capsaicin

TRPV1 (capsaicin) receptors perceive different sensory stimuli. TRPV1 receptors are activated by temperatures >42°C, pH <5.9 and capsaicin.

» Symptom: Burning

» Mechanism: TRPV1 – receptors, Peripheral sensitization

» Entities in Peripheral neuropathic pain

» Dose range: 8%, one application

» Add on therapy, few local side effects, no interactions

Mechanisms of central sensitization in the spinal cord: Ca-channel expression, Deficient descending inhibition and Active descending facilitation.

» Ca-channel expression: clinical phenomena

» Symptom: Mechanical allodynia

» Mechanism: Ca-channels, Central sensitization

» E.g., Gabapentin, Pregabalin, Ca-channel modulators

» Agents: Pregabalin

» Dose range: 150-600mg

» Few side effects, few interactions, good effects on sleep.

Treatment guidelines

Neuropathic pain therapy: Oral/systemic medication (Antidepressants, Antikonvulsants (Ca), Antikonvulsants (Na), Tramadol, Opioids, Tapentadol) + Topical therapy (Lidocaine, Capsaicin) but no NSAIDs.

Summary

» To use conventional analgesics

» To use SSRI for pain treatment

» To indicate topical treatment in central pain states

» To recommend opioids as first or second line.

4. Immune-mediated small fiber neuropathy: classification, diagnosis and treatment

(Speaker: Janneke Hoeijmakers, EAN 2022)

Immune-mediated neuropathies are the heterogenous groups caused by immune reaction of peripheral nerves and Immune-mediated neuropathies classified in acute onset, chronic, axonal and demyelinating. There is no intension between immune mediate small fibre neuropathy.

It possesses sensory symptoms involves feeling of needle, warmth or heat on hands or foot, loss of pain sensation, allodynia, etc. The diagnosis can be made by clinical picture and examination by abnormal skin biopsy.

The autoimmune disease related to small fibre neuropathy are Sjogren syndrome, sarcoidosis and celiac disease. Novel autoantibodies idiopathic SFN includes MX1: Neuropathic pain (mice) and Back pain, DBNL: Alzheimer disease and KRT8: Neuropathic pain CIDP.

Immune-mediated SFN Treatment include Intravenous immunoglobulins (IVIG) shows good results and also some studies showed good effect in pain. The method includes screening and randomization with IVIG and placebo groups. Screening period was 7 to 10 days, treatment period was 12 weeks and follow-up period were 3 months. The primary outcome was pain Intensity, Numeric Rating Scale Responder: ≥ 1-point improvement on the PI-NRS for 12 weeks treatment compared to baseline. The results suggested that IVIG treatment had no significant effect on pain in patients with painful idiopathic SFN.

Summary

» The sensory pattern of immune-mediated SFN is mostly non-length dependent.

» Immune-mediated SFN can develop in patients with autoimmune diseases, when specific auto-

antibodies are present, post-infectious and post-vaccination.

» The exact underlying pathophysiological mechanisms in patients with immune-mediated SFN are often unclear.

» Randomized controlled trials in immune-mediated SFN are lacking

» IVIG treatment has no significant effect on pain in painful idiopathic SFN.

5. Does small fiber neuropathy contribute to chronic muscle pain in

patients with myotonic dystrophy?

(Source: V. Schmitt, P. Bäumler, D. Irnich, et al. Does small fiber neuropathy contribute to chronic muscle pain in patients with myotonic dystrophy? Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Myotonic dystrophy (DM), one of the most common adult muscular dystrophies is commonly associated with chronic myalgia, however, the pathophysiology remains unclear. This study sought to investigate whether small fiber neuropathy contributes to chronic pain in DM patients.

The study included DM1 and DM2 patients (18-65 years) with myalgia. Exclusion criteria were diabetes mellitus or polyneuropathy. Patients completed three pain questionnaires, neurological examination, nerve conduction study, quantitative sensory testing (QST) and skin biopsy. QST data were compared with 30 gender- and age-matched healthy controls.

The investigators recruited 32 DM2 and 21 DM1 patients. In comparison to DM1, DM2 patients showed higher pain related disability (p=0.026), higher pain interference (p=0.012), described pain more often as radiating (78% vs 25%, p<0.001) and suffered more of chronic constant pain (38% vs 25%) rather than pain attacks as in DM1 (55% vs 25%). In QST, we found multiple differences between DM1 and DM2 and between DM and controls. DM2 patients were characterized by a loss in cold, warm, mechanical and vibration sensitivity, while DM1 patients showed signs of mechanical hyperalgesia (lower mechanical pain threshold, higher mechanical pain sensitivity). Both DM patient groups showed increased pressure pain sensitivity. IENFD was reduced in 63% of DM1 patients and in 50% of DM2. this correlated with age (p=0.050) but, interestingly, not with QST data.

This study shows the presence of loss in detection sensitivity and gain in pain sensitivity in patients with myotonic dystrophy, as well as reduced IENFD. Ongoing analyses will further examine how these abnormalities correlate with the severity and quality of pain.

6. Vitamin B12 deficiency-related neurological manifestations: 5 years

of experience in a Portuguese tertiary center

(Source: C. Fernandes, J. Sousa-Baptista, A. Geraldo, et al. Vitamin B12 deficiency-related neurological manifestations: 5 years of experience in a Portuguese tertiary center. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Vitamin B12 (vitB12) is essential in cellular metabolism and plays a significant part in the nervous system. Neurological manifestations such myelopathy, peripheric neuropathy, optic neuritis or neuropsychiatric symptoms, for example cognitive deterioration are seen inn almost 40% of the patients diagnosed with B12 deficiency. Clinical, laboratorial and imagological characterization of patients with neurological manifestations related to vitB12 deficiency (<187 pg/ml). A retrospective and observational study included patients followed at Neurology Department between January 2016 and May 2021.

Overall, 72 patients (54.2% female) were included with a mean age of diagnosis of 70.9±14.1 years. The most common neurological manifestation associated with vitB12 deficiency was cognitive deterioration (70.8%) followed by peripheral neuropathy (15.3%) and myelopathy (12.5%). Patients with cognitive impairment had a mean MMSE score of 21.4±5.5 points. 90.8% and 87.7% of patients had hemoglobin and MCV values within the reference values, respectively. 58.2% of the cranioencephalic CT scans revealed signs of atrophy. There was significant statistically difference between the value of serum vitB12 and different neurological manifestations. Post-hoc tests indicated a difference in the mean value of vitB12 measure between patients with myelopathy versus peripheral neuropathy or neuropsychiatric manifestations. There was no significant statistically correlation between the vitB12 value and the hemoglobin value.

VitB12 deficiency is associated with different neurological syndromes, even in the absence of appreciable hematological alterations. Since it is a reversible and preventable cause of neuro logical impairment, early diagnostic suspicion and treatment are essential for better outcome.

7. Peripheral neuropathy and MOG-IgG: a clinical and neuropathological retrospective study

(Source: A. Dinoto, N. Licciardi, M. Reindl, et al. Peripheral neuropathy and MOG-IgG: a clinical and neuropathological retrospective study. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Evidence suggests that peripheral nervous system is seldom involved in myelin oligodendrocyte glycoprotein antibodies (MOG-Abs). A study aimed to test MOG-Abs in patients with undetermined peripheral neuropathy (PN).

Consecutive patients with available sural nerve biopsy and paired serum sample were retrospectively identified (January, 1st 2016-November, 1st 2021) and tested for MOG-Abs with live cell-based assay (CBA). Patients with antibody titre ≥1:160 (secondary H+L antibody) and selective MOG-IgG presence (IgG-Fc predominance) were considered MOG-IgG positive. All positive samples were analysed with immunohistochemistry and CBAs for antibodies against Neurofascin-155 and Contactin-1. Clinical and neuropathological data were collected through clinical reports.

Among 163 patients, 5 (3%) resulted positive for predominantly IgG MOG-Abs (median titer 1:320, range 1:160– 1:5120), none showed other concomitant antibodies. Median age was 74 years-old (range 55–81), median disease duration was 60 months (range 1–167), 60% of patients were female. Of these, 4/5 cases had clinical features suggestive of acute (n=1) or chronic (n=3) inflammatory demyelinating neuropathy, 2/5 fulfilled the criteria of combined central and peripheral demyelination (CCPD) whilst 3/5 had isolated PNS involvement. Neuropathological findings showed mixed axonal-demyelinating features in 2/5, predominant demyelination in 3/5 cases. Other neuropathological hallmarks included paranodal demyelination (n=3), myelin outfoldings (n=4), slight inflammatory infiltrates (n=3), onion bulbs (n=3), clusters of regeneration (n=4).

MOG-IgG can be detected in patients with isolated PN or CCPD. Clinical and neuropathological features are suggestive for demyelination and slight inflammation. Further studies should include larger cohorts of patients to elucidate the utility of MOG-Abs testing in PN.

8. Photobiomodulation therapy for the prevention of chemotherapy- induced peripheral neuropathy (NEUROLASER trial)

(Source: J. Lodewijckx, J. Robijns, M. Claes, et al. Photobiomodulation therapy for the prevention of chemotherapy-induced peripheral neuropathy (NEUROLASER trial). Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Taxanes are well known to cause chemotherapy-induced peripheral neuropathy (CIPN). To date, there are no evidence- based measures to prevent or minimize CIPN. Photobiomodulation (PBM) therapy is based on the application of (near)-infrared light on target tissue to stimulate cell repair processes and reduce pain and inflammation. The aim of this trial was to evaluate if PBM can prevent sensory symptoms associated with CIPN and enhance the patients’ quality of life (QoL).

A RCT with 32 breast cancer patients that underwent taxane treatment was performed at the Jessa Hospital (Hasselt, Belgium). Patients were randomized to receive PBM or placebo treatments (2x/week) starting at first until the last week of their chemotherapy (CT). The patients’ QoL and their neurotoxicity symptoms were assessed by the FACT/ GOG-NTX questionnaire. A higher overall score indicates a better QoL. Measures were collected at four time points.

Mixed ANOVA revealed a significant difference in the group by time interaction for the FACT/GOG-NTX total score (p=0.036) with a higher overall score in the PBM group. Specific questions of the FACT/GOG-NTX regarding numbness in hands and feet were analyzed separately. A significant increase in the severity of numbness in hands and feet over time was observed in the control group (ps=0.000), whereas it remained constant in the PBM group (ps≥0.173).

Based on these results, PBM seems to reduce the development of CIPN resulting in a better QoL. These results must be interpreted with caution because of the limited sample size. Further research in a larger patient population is necessary.

9. Cannabinoids for painful dystonia in corticobasal syndrome: a report

of three patients.

(Source: G. Rizzo, P. Avoni, V. Donadio, et al. Cannabinoids for painful dystonia in corticobasal syndrome: a report of three patients. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Corticobasal syndrome (CBS) comprises of limb dystonia, is frequently associated with intense pain that is often difficult to treat despite numerous therapeutic attempts. Cannabinoids are increasingly used to treat pain and some reports suggest a potential benefit in dystonia. The researchers sought to assess the efficacy of cannabinoids in painful dystonia of CBS patients.

Three patients with CBS complained painful limb dystonia. All three patients were treated with different pain medication, without achieving satisfactory pain relief. Therefore, we added cannabis-based oily solutions to the therapy, collecting Numeric Rating Scale (NRS) values for pain before and after three months from the start.

Case 1

Case 1 presented main involvement of the right arm. Her therapy included botulinum toxin injections, amitriptyline, clonazepam and baclofen. She started Bedrolite® oil (THC 1%, CBD 9%, 20 drops/die) therapy, and the NRS value changed from 8 to 3.

Case 2

Case 2 presented main involvement of the left arm. Her therapy included botulinum toxin injections, amitriptyline, clonazepam, baclofen and oxycodone. She started Bediol® oil (THC 6.5%, CBD 8%, 25 drops/die) therapy, and the NRS value decreased from 10 to 1.

Case 3

Case 3 presented main involvement of the right leg. His therapy included botulinum toxin injections, clonazepam, pregabalin, baclofen and oxycodone. He started Bedrolite® oil (60 drops/die) therapy, and the NRS value decreased from 9 to 2. The therapy was well tolerated in all patients.

Cannabinoids should be considered as a useful add-on therapy for painful dystonia in CBS patients.

10. Antibody Response after COVID-19 Vaccination in IVIg Dependent Immune Neuropathies: An Observational Study

(Source: M. Svacina, A. Meißner, F. Schweitzer, et al. Antibody Response after COVID-19 Vaccination in IVIg Dependent Immune Neuropathies: An Observational Study. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

A prospective study sought to assess the prevalence of anti-SARS-CoV-2 antibodies in therapeutic immunoglobulin and their impact on the immune response to COVID-19 mRNA vaccine in patients with intravenous immunoglobulin (IVIg) dependent immune neuropathies.

A total of 46 different IVIg and subcutaneous IgG (SCIg) samples were analyzed for anti-SARS-CoV-2 IgG by ELISA and chemiluminescent microparticle immunoassay (CMIA). Blood sera of 16 immune neuropathy patients (mean age 65±16 years, 25% female) were prospectively analyzed for anti-SARS-CoV-2 IgA, IgG, and IgM before and one week after IVIg infusion subsequent to consecutive COVID-19 mRNA vaccine doses and 12 weeks thereafter. Forty-two healthy subjects were recruited as a control group (mean age 42±13 years, 83% female).

A total of 52 percent of therapeutic immunoglobulin samples contained anti-SARS-CoV-2 IgG. All patients with immune neuropathies showed anti-SARS-CoV-2 IgG reactivity after COVID-19 vaccination. Anti-SARS-CoV-2 IgA titers significantly decreased 12–14 weeks after vaccination (p=0.02) whereas IgG titers remained stable (p=0.2). IVIg did not affect anti-SARS-CoV-2 IgA/IgG serum titers in immune neuropathies (p=0.69). IVIg-derived anti-SARSCoV-2 IgG did not increase serum anti-SARS-CoV-2 IgG titers (p=0.67).

11. The Spectrum of Bilateral Optic Neuropathy: a case series

(Source: M. Gilligan, S. Tobias, L. Manahan, et al. The Spectrum of Bilateral Optic Neuropathy: a case series. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Bilateral optic neuropathies may be associated with wide range of underlying etiologies. The differential diagnosis includes autoimmune, infectious, toxic, and genetic causes. A prospective study conducted at a tertiary care centre aimed to review cases of bilateral optic neuropathy attending a neurology center and describe the underlying clinical characteristics, diagnoses and investigations performed in this cohort.

Patients presenting to a tertiary referral center in Dublin, Ireland, between January 2011 and August 2021 with sequential or simultaneous bilateral optic neuropathy were included. Hospital coding information was searched for Optic Neuritis, Optic Neuritis with demyelination and Other Optic Neuropathies.

A total of 33 patients with bilateral optic neuropathy were identified. The majority of patients were male (64%). The mean age at onset was 35 (range 8–63). The most common diagnoses included myelin oligodendrocyte

IVIg does not impair the antibody response to COVID-19 mRNA vaccine when administered a minimum of two weeks after each vaccine dose. The infusion of current IVIg preparations that contain anti-SARS- CoV-2 IgG does not enhance serum anti-SARS-CoV-2 IgG reactivity

glycoprotein antibody disease (MOGAD) (n=6) and multiple sclerosis (n=6), followed by neuromyelitis optica (n=3) and neurosyphilis (n=3). Other etiologies included systemic sarcoidosis with neurological involvement, Lebar’s hereditary optic neuropathy, nutritional deficiency and chronic relapsing inflammatory optic neuropathy (CRION). In six patients (18%) no diagnosis was reached despite extensive investigations.

MRI Brain was performed in 97% of patients and was abnormal in 37%. MRI orbit was performed in 73% of patients with optic nerve abnormalities detected in 75%. CSF sampling was performed in 78% of patients and abnormal in 46%.

12. Facial neuropathy secondary to cocaine use: an infrequent and

refractory entity

(Source: P. Garrido Jiménez, A. Lorenzo Montilla, M. Alarcón Morcillo, et al. Facial neuropathy secondary to cocaine use: an infrequent and refractory entity. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

A rare type of drug-resistant facial neuralgia associated with non-traumatic causes is the trigeminal terminal branch neuropathy, which is often difficult to suspect. Presented here is a case of infraorbital and external nasal dysautonomic neuropathy of otorhinolaryngologic etiology, with excellent response to anesthetic infiltration.

A 28-year-old man, regular consumer of cocaine, initiated a paroxystic intense burning pain on the nasal wing radiated to infraorbital and cygomatic alternating bilateral regions and dysautonomia (local edema and erythema, eye redness and bilateral tearing). This clinical presentation was associated to millimetric ulcers in both nostrils with posterior nasal septum perforation and formation of a bacterial abscess. Blood tests including herpes virus serology and autoimmunity tests delivered normal results. No pulmonary infiltrates and pleural effusion were observed on the chest x-ray. Vascular damage was not found on the cerebral magnetic resonance imaging with angiography. The facial/sinus computerized tomography only showed a deviation of the nasal septum.

Figure 1: Dysautonomia in infraorbital and external nasal nerve territories

Bilateral optic neuropathy is an uncommon clinical presentation with a diverse range of etiologies. This cohort revealed a male preponderance with inflammatory causes predominating. However, almost one fifth of cases remained idiopathic.

The patient started treatment with gabapentin, amitriptyline, eslicarbazepine acetate and intranasal lidocaine, with no favourable results. Afterwards he initiated local infiltrations with 1 cm3 of 2%-lidocaine in each infraorbital and external nasal nerves with complete resolution of pain and remaining asymptomatic for two months.

This case report highlights the importance of an adequate otorhinolaryngologic examination when searching for non-traumatic causes of trigeminal terminal branch neuropathy, given its anatomic location and bilateral crossed innervation (nasal septum anomalies, rhinosinusitis or granulomatosis with polyangiitis) as well as its frequent refractoriness to treatment, with an optimum medium-term response to anesthetic infiltration.

13. Fiber neuropathy following SARSCOV-19 vaccination. A case series

(Source: A. Ezaru, A. Puma, L. Villa, et al. Fiber neuropathy following SARSCOV-19 vaccination. A case series. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Small fiber neuropathy (SFN) is a polymorphous disease affecting thin nervous fibers conducting temperature and pain sensations and involved in autonomic transmission. Etiology is diverse and remains elusive in 70% of cases.

We describe a case series of 6 patients who developed symptoms of SFN following SARS-COV-19 vaccination. Neurologic examination was normal whilst paraclinical results were consistent with SFN. Confirmation by skin biopsy was obtained in 4 cases.

Six patients, 5 female and 1 male, ages 31, 34, 39, 42, 44 and 62 years, consulted our department with intense pain and numbness involving the arms and legs 2 to 15 days following SARS-COV-19 vaccination. Neurologic examination was normal. A preliminary diagnostic protocol comprising autoimmune, metabolic, infectious and inflammatory panel, cerebral and spinal cord magnetic resonance imaging and electromyography was normal. Functional neurophysiologic testing showed reduced activation of fibers involved in sweat gland control indicating SFN. Skin biopsy of distal calf and thigh in 4 patients, three female and one male, showed rarefaction of thin intraepidermic nerve fibers in a non-length dependent manner, allowing for a diagnosis of SFN.

Whereas autoimmune, infectious, metabolic, toxic and genetic causes are well described in SFN, evidence of possible association with vaccination is confounding. Given their small caliber and richness of surface antigens, small nervous fibers are vulnerable to a wide spectrum of disease. Immunologic factors intervening on a predisposing substrate could be a hypothesis for the mechanism involved in development of SFN following SARS-COV-19 and possibly other vaccination

14. Young-onset Parkinsonism and neuropathy in FIG4 gene mutations

(Source: L. Silva, J. Freixo, A. Brandão, et al. Young-onset Parkinsonism and neuropathy in FIG4 gene mutations. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Patients bearing pathogenic variants in PARK2 or POLG often suffer from young-onset Parkinsonism (YOP) and peripheral neuropathy (PN). Biallellic mutations in FIG4 were originally described in Charcot-Marie-Tooth disease 4J (CMT4J), and more recently Yunis-Varon syndrome and Parkinsonism+CMT4J. Described here is a patient with YOP and PN, with compound heterozygous mutations in FIG4.

Descriptive analysis of clinical, imaging, electrophysiological, genetic findings.

A 39-year-old male, born of nonconsanguineous parents, presented with a one-year history of hands rest tremor and gait impairment. He described pes cavus and hammertoes since childhood and no family history of neurological disorders. On examination there was facial hypomimia, left predominant rest and re-emergent postural tremor, cogwheel rigidity and bradykinesia. Additionally, he had decreased vibration sensation, difficulties in walking on heels and bilaterally decreased arm swing. Brain MRI disclosed small pallidal hypointensities; DaTSCAN a marked bilateral presynaptic dopaminergic deficit. Electromyography revealed a sensory-motor polyneuropathy with severe distal-toproximal axonal loss and demyelinating features in some slightly preserved nerves. NGS panel, based in WES, for 1410 genes related with neurological disorders, identified two variants in FIG4 gene [(NM_014845.5) – c.122T>C (p.(Ile41Thr)) and (NM_014845.5) – c.1519dup (p. (Tyr507Leufs*10))]. He is currently under levodopa/ rotigotine with a good response.

This is the sixth reported patient with Parkinsonism and PN with FIG4 mutations. The majority had young-onset and, the ones who were treated, clinical improvement under antiparkinsonian drugs. NGS sequencing techniques have greatly contributed to the characterization of YOP and expansion of the classical genotype-phenotype correlations.

15. Optic neuropathy secondary to Herpes Zoster virus

(Source: L. Ruiz-Escribano Menchen, L. Quiros Illan, E. Diaz Fernandez, et al. Optic neuropathy secondary to Herpes Zoster virus. Abstract presented at: 8th Congress of the European Academy of Neurology, June 25-28, 2022, Vienna, Austria).

Herpes zoster ophthalmicus occurs due to the reactivation of the latent varicella-zoster virus due to the involvement of the ophthalmic branch of trigeminal nerve (V1). It has diverse presentations that include both anterior and posterior segment pathology. Herpes Zoster optic neuropathy (HZON) has been reported in 1.9% HZO affected eyes.

A 62-years-old man, without relevant medical history, presented to the emergency department with left red eye symptoms and vesicles in left V1 territory. He was diagnosed of herpetic keratoconjunctivitis by ophthalmologist and started treatment with oral acyclovir and topical corticosteroids. One week later he was derivated to the neurologist because of left papilledema. Visual acuity was normal in both examinations.

Figure 2: Left herpetic vesicules in V1 territory

The patient had a normal Brain CT. Cerebrospinal fluid (CSF) analysis: 131 leukocytes (98% lymphocytes), mild hyperproteinorrhachia (66.7mg/dl) without glucose consumption. Polymerase Chain Reaction (PCR)

HZON is a rare complication of HZO that may present either in papillitis or retrobulbar form and habitually occurs simultaneously with other ocular complications. It develops with a mean of 14 days after initial rash. Visual recovery is variable and MRI-restricted diffusion of the optic nerve can predict a poor recovery. In the present case, the patient had an excellent visual outcome because of the fast diagnosis of papilledema with positive PCR to VZV in CSF (which is exceptional). This case emphasizes the importance of the early diagnosis to start a prompt treatment with both systemic acyclovir and topical or systemic corticosteroids.

was positive to VZV. Orbital and brain MRI were normal. He completed 2 weeks of intravenous acyclovir without visual impairment.

16. Peripheral neuropathy following COVID-19 mRNA vaccination – 2 Case Reports

Author: Florin P et al, Cantonal Hospital St. Gallen, Department of Neurology, St. Gallen. Switzerland

Introduction

Author described two recent cases of peripheral neuropathy reported after vaccination with mRNA SARS-CoV2 vaccine.

Case 1:

A 67-year-old man with hypertension and hyperlipidemia developed acute and severe neuropathic shoulder pain 8 days after the second vaccination dose of COVID-19 vaccine in the ipsilateral deltoid muscle. A causative trauma and other differential diagnoses were denied. NSAIDs showed no effect, but corticosteroids improved the pain. Subsequently paresis of the left proximal shoulder muscles occurred, and EMG showed axonal damage.

Case 2:

A 60-year-old female with no medical history developed weakness of left hand extension 4 days after the first vaccination dose of COVID-19 vaccine in the ipsilateral deltoid muscle. Neurological examination showed a mild paresis of the radial innervated muscles in the forearm and reduced sensitivity of the dorso-radial area of her hand. Nerve-conduction-studies demonstrated a conduction block of the radial nerve proximal to the elbow, concomitant with focal swelling detected by high-resolution nerve ultrasound.

Conclusion

The two cases showed a temporal and local association (ipsilateral injection) of peripheral neuropathies after vaccination with mRNA COVID-19 vaccine. Similar case reports are published. However, temporal association is not equal to causal association and can ideally be investigated by prospective randomized trials, which is unethical in the pandemic situation. Therefore, prospective register studies, case series and case reports must act as a substitute. However, due to underreporting or insufficient timely data processing a large body of information is missing.

Figure 1: High-resolution nerve ultrasound of Patient 2 On the right side the focal swelling of the left N. radialis on the upper arm (5.7 mm2). On the left side the right N. radialis on the upper arm.

17. Clinical and electrophysiological characteristics of COVID and post COVID polyneuropathies in adults and paediatrics

Author: Haidy Elshebawy et al, Department of Neurology, Cairo University, Cairo, Egypt Introduction

COVID-19 associated neuromuscular disorders are the second most commonly encountered neurological complications, especially Gullian barre syndrome (GBS).

Aim: To describe covid -19 patients who presented or complicated with different forms of polyneuropathy in adults and pediatrics in first and second waves of the pandemic and their outcome with different therapeutic regimens.

Subjects and Methods

This study was conducted on 52 patients presented by different forms of polyneuropathy complicated COVID 19 infection in different age groups, Patients were divided into two groups, group (A) and group (B) in first and second waves respectively. Electromyography (EMG) and nerve conduction (NC) studies were done to all the participants.

Results

Regarding the comparison between the two waves of the pandemic, there Is a significant difference between the 2 groups regarding the age with P value <0.05.(fig 1), but there was no significant difference between both waves regarding the type of polyneuropathy (P value 0.193) and the outcome of the recovered patients (P value 0.084).

Fig 1 Regarding the comparison between adults and pediatric groups, authors found that the picture of neuropathy affecting the pediatric mainly is the AIDP rather than different types of neuropathy affecting the adults group with a significant difference between the two groups (P value <0.05).(fig 2) ,while there was no significant difference regarding the outcome of the neuropathy in treatment between the adult and pediatric groups (P value 0.129).

Figure 1: Comparison between both waves regarding age groups

Figure 2: Comparison between the adults and pediatric groups according to type of neuropathy

Conclusion

Author concluded that there is a need to gain a better understanding of the underlying pathophysiology and therapeutic options of (GBS) related to COVID-19, which will have an impact on the treatment of the COVID related

18. Peripheral neuropathy due to neuroborreliosis: Insensitivity for CXCL13 as early diagnostic marker

Author: Kristina Scigulinskyl et al, Department of Neurology, Landesklinikum Mistelbach-Ganserndorf, Mistelbach, Australia

Introduction

‘Lyme neuroborreliosis’ (LNB) develops in 10-15% of all adult Borrelia infections. The most common manifestations are meningoradiculitis and cranial neuritis. Rarer neurological complications include brain and spinal cord involvement, cerebral vasculitis, and peripheral neuropathies. The intrathecal antibody response against Borrelia is negative in 10-30% when symptom duration is less than 6 weeks.1’2 This underscores the need for a more accurate early diagnostic marker. The B cell chemoattractant CXCL13 is a promising biomarker in LNB. A recent meta-analysis revealed a diagnostic sensitivity and specificity of CXCL13 in cerebrospinal fluid (CSF) of 89% and 96%, respectively.’

Aim

Author reported the case of peripheral neuropathy caused by Lyme Neuroborreliosis, in which CXCL13 in CSF did not aid clinical suspicion and earlier diagnosis.

Case report

A 69-year-old woman living in Eastern Austria, a region endemic for borreliosis, had noticed patchy areas of tingling and numbness distal to her left knee for the last 4 weeks. She did not recall a trauma to her leg and did not report meningeal or radicular symptoms. She could not recall a tick bite or erythema. Her medical history included hypertension and hypercholesteremia.

Clinical exams, neurophysiology and imaging:

On neurological examination, sensory symptoms were intermittent and did not follow a dermatomal distribution. Nerve conduction studies (NCS) of the upper and lower extremities were unremarkable.., and cerebral or brain stem infarction was ruled out on brain/cervical spine magnetic resonance imaging (MRI). Treatment with pregabalin was started, which only relieved her sensory symptoms slightly.

Lab testing: Exam of CSF did not reveal any abnormalities except for oligoclonal bands (OCB). CXCL13 in CSF was below the detection limit. Serum Borrelia IgG antibodies were elevated.

Follow-up:

14 days later, she reported a further increase in sensory symptoms and new-onset burning pain in the left leg during the night, which partly improved with physical activity.

Day 33:

She presented to the Emergency Room after pain progressed and a left-sided foot drop had occurred, at that time grade 4 according to the Medical Research Council (MRC) grading. NCS revealed an incomplete nerve conduction block of the peroneal nerve at the head of the fibula level. An orthopedic examination was unremarkable.

Day 50:

The foot drop had progressed to plegia. Needle electromyography (EMG) of the clinically affected muscles showed fibrillation. The potentials and reduced recruitment, consistent with a subacute neurogenic process. The neurophysiological findings were consistent with re a postganglionic asymmetric mixed axonal and demyelinating sensorimotor neuropathy. She was started on oral prednisolone on empirical ap grounds, but this was terminated after pain was only minimally lessened and motor deficits were unaltered.

Day 54:

A re-tap revealed a lymphomononuclear pleocytosis of 13 cells/u1 (normal range, <5/0). Autochthonous synthesis of total immunoglobulin M (IgM, 6.5%) and Borrelia-specific IgM antibodies in CSF (antibody index (Al) 41.6 (<0.3)), and for Borrefia-specific IgG (Al 27.1) was found. This time, CXCL13 in CSF was 44 pg/ml (cut-off <30 pg/ml, according to Euroimmun, Lubeck, Germany), which further supported the diagnosis of isolated peripheral LNB neuropathy. Other infectious agents and autoimmune conditions were excluded in an extensive search with serology and PCR.

Treatment and further course:

The 14-day treatment with intravenous ceftriaxone led to a rapid improvement of the pain. The recovery of motor deficits has been incomplete so far; the MRC grade was 3-4 at the outpatient clinic visit on day 99.

Conclusion

This case of peripheral LNB neuropathy revealed the insensitivity of CXCL13 in the CSF to aid in earlier diagnosis. Our observation reinforces the need for a higher index of suspicion in endemic areas to initiate a re-tap to corroborate the diagnosis and facilitate appropriate treatment for this rarer manifestation of LNB.

19. Peripheral neuropathy in myotonic dystrophy type 1 patients

Background

Myotonic dystrophy type 1 (DM1) is a multisystem disease that characterized by wide spectrum of symptoms. In addition to classic neuromuscular features some patients have signs of polyneuropathies.

Aim: To analyze the frequency and type of peripheral nerves abnormalities among DM-1 patients.

Methods

The sample for this study included 21 adult patients with DM1. Nerve conduction study was performed on tibial, sural, peroneal, median, radial and ulnar nerves of both limbs.

Results

» None of the patients had diabetes mellitus or other endocrine pathology. Decreased SNAP were detected in right and left lower limbs in 38.1% and 33.3% of cases, respectively. 4 MD1 patients showed an absent of SNAP. Axonal sensory polyneuropathy was observed in 61.9% of patients. A decrease in the amplitude of the sural SNAP was related to a decrease in tibial CMAP on both sides (R=0.484, p=0.026/R=0.480, p=0.044)

» 15 patients had electrophysiological signs of cubital tunnel syndrome, 6 -fibular tunnel syndrome, 3 – tarsal syndrome.

Conclusions

» » »

The study confirms presence of axonal sensory and sensorimotor polyneuropathy of the lower limbs in patients with DM1.

Due to the absence of uncompensated metabolic diseases, it can be assumed that identified abnormalities are primary.

The results show the presence of tunnel compression neuropatlues, which can aggravate the severity of clinical manifestations.

20. The role of beta-NGF in the maintenance of chronic neuropathic pain in post-traumatic neuropathies and plexopathies

Author: Dr O Borodai,

Introduction

Plastic rearrangements of neurons during their development and life are largely regulated by trophic factors, among which nerve growth factor (NGF) is of particular interest, which is involved in neuronal differentiation. The aim of this study was to investigate the effect of beta-NGF in the maintenance of chronic neuropathic pain syndrome in patients with post-traumatic neuropathies and plexopathies.

Methods

Authors examined 93 men aged 21 to 59 years with neuropathies and plexopathies, who were divided into 3 groups. All patients underwent neurological examination, electroneuromyography. Quantitative determination of beta-NGF in whey was carried out by enzyme immunoassay I year after the onset of the disease.

Results

As a result of the study, statistically significant differences (p<0.05) in the content of beta-NGF. In group I of patients with compression-ischemic neuropathies and plexopathies, the level of Beta-NOF was 83.6[42; 335.4]pg /nil, in group II of patients with post-traumatic non-gunshot neuropathies and plexopathies 64.65[25; 97.5Jpg/ml, in patients of group HI with post-traumatic gunshot neuropathies and plexopathies, which are accompanied by chronic neuropathic pain was 303[35.2; 504.5Jpg/ml, which indicates the ongoing process of chronic inflammation.

Figure 1: Quantitative contenct of nerve growth factors (Beta-NGF) in the study group (pg/ml)

Conclusion

The determination of the content of beta-NGF in patients with gunshot injuries of nerves and plexuses improves understanding of the chronicity of neuropathic pain and opens up the possibility of searching for complex therapy.

21. IVIg responsive neuropathy associated with the treatment of cutaneous T-cell lymphoma with Brentuximab

Author: Dr. Sofia Lopes et al. neurology department, Hospital de Braga, Portugal

Introduction

Brentuximab vedotin (VD) is an antibody that can be used to treat relapsed CD30+ cutaneous 1-cell lymphoma. latrogenic peripheral neuropathy has been described in several case series, presenting most commonly with demyelinating features. Author describe a case of sensorimotor neuropathy following brentuximab treatment.

Case

» 44-year-old man

» Two year history of recurrent cutaneous 1-cell lymphoma (mycosis fungicides) chronological order Psoralen ultraviolet A vincristine and prednisone (CHOEP) cyclophosphamide, Treatments in Retinoid + doxorubicin, etoposide,

» One year after recurrent BV treatments, the patient complained about: Numbness in both legs I Difficulty in climbing stairs, rising from a seated position and buttoning

» Neurological examination showed: Tetraparesis with distal predominance I Absent osteotendinous reflexes I Distal position and pain sensory impairment

» Complementary exams: CSF showed discrete albuminocytologic dissociation I Spinal MRI was unremarkable I Nerve conduction studies showed severe sensorimotor symmetric polyneuropathy predominantly affecting lower limbs, with axonal involvement and evidence of demyelination

» BV was discontinued and the patient started treatment with IV immunoglobulin and physical rehabilitation with strength improvement

Cyclophosphamide, doxorubicin, etoposide, vincristine and prednisone (CHOEP)

Bexarotene+ interferon- alpha

Treatments in chronological order

Retinoids +Psoralen ultraviolet A

Brentuximab vedotin

Conclusion

Severe polyradiculoneuropathies, resembling CIDP, can appear during treatment with BV and management with IVIg may be effective.

22. Patient Characteristics from the NEURO-TTRansform Study of Eplontersen in Transthyretin Amyloidosis Polyneuropathy

Author: Laura Obici et al

Introduction

Hereditary transthyretin amyloidosis (ATTRv [v for variant]) is a rare, severe, progressive, debilitating, and ultimately fatal disease caused by systemic accumulation of transthyretin (TTR) amyloid fibrils, leading to multiorgan failure’ – TTR is primarily synthesised by the liver’

Eplontersen (ION-682884) is an investigational ligand-conjugated antisense (LICA) oligonucleotide designed to degrade TTR mRNA in the liver, inhibiting TTR protein synthesist

The NEURO-TTRansform trial (NCT04136184, EudraCT 2019-001698-10) is an ongoing phase 3 study designed to evaluate the efficacy and safety of eplontersen compared with historical control (placebo arm in the NEURO-TTR trial [NCT01737398]) in patients with ATTRv polyneuropathy (ATTRv-PN)4-6; an inotersen reference group (6:1 randomisation of eplontersen:inotersen) was included to confirm sufficiently comparable disease progression and treatment response patterns between NEURO-TTRansform and NEURO-TTR.

Patient Population

This international, open-label study is being conducted in adult patients with familial amyloid polyneuropathy Stage 1 or Stage 2, a documented TTR sequence variant, and signs/symptoms consistent with polyneuropathy (Table 1)

Patient Characteristics

The NEURO-TTRansform study includes 168 patients across 15 countries (Figure 1); 144 patients are randomised to eplontersen and 24 to inotersen – 26 patients (15.5%) are in North America, including Canada and the United States – 78 patients (46.4%) are in South America/Australia/Asia, including Argentina, Australia, Brazil, New Zealand, and Taiwan – 64 patients (38.1%) are in Europe, including Cyprus, France, Germany, Italy, Portugal, Spain, Sweden, and Turkey

Among the European subpopulation, patients have a mean age of 50.3 years; the majority of patients are male (82.8%) and white (98.4%): Most patients (86%) have a Polyneuropathy Disability Score of I or II (Figure 2) – The most common TTR sequence variant is V30M, occurring in 78.1% of the European subpopulation (Figure 2) – Most patients (80%) are at New York Heart Association functional classification I (Figure 2)

Conclusion

The baseline characteristics of patients treated with eplontersen or inotersen in the NEURO-TTRansform European subpopulation are representative of the trial eligibility criteria and contemporary clinical practice.

23. Bilateral optic neuropathy secondary to Vitamin B12 deficiency

Author: Sai A Nagaratnam et al, department of Neurology, Gosford hospital, Australia

Introduction

Optic neuropathy is a rare presentation of Vitamin B12 deficiency. In countries such as Australia with calorie-dense diets, neurological complications of Vitamin B12 deficiency are rare. It presents as progressive, bilateral visual loss.

Methods

A 29-year-old male presented with progressive, painless central and colour visual loss over 2-3 weeks. He had no previous ocular history. He also developed balance issues and subjective peripheral sensory disturbance in both hands and feet. He smoked cannabis and tobacco and did not drink alcohol. There was a maternal history of pernicious anaemia. He had central visual scotomas with reduced visual acuity of 6/60 on the right and 6/45 on the left with normal power and reflexes and intact pmprioception. MRI Brain and Spine was normal with no suggestion of demyelination. Bloods showed a normal haemoglobin with macrocytosis. Both active and total B12 were low at 27pmoUL (>35) and 82pmol/L (135-650) respectively with a normal folate level of 9. I nmol/L (>7).

Visual evoked potentials showed slow conduction bilaterally. Particularly in the anterior optic pathways, worse on the left (Figure la & I b). Nerve conduction studies showed a sensory neuropathy affecting the upper limbs.

Results

He received 3 doses of ling intramuscular vitamin 812 replacement. Repeat testing showed an active 1312 level of >128pmol/L. His vision gradually improved over the next 6-12 months.

Figure la: Left full field visual evoked potentials showing an N75 of 119 msec, P100 of 142 msec and an NI45 of 167 MCC.

Figure lb: Right full field visual evoked potentials showing an N75 of 107 msec, P100 of 132 msec and an N 145 of 154 msec.

Conclusions

Bilateral optic neuropathy is a rare presentation of Vitamin B12 deficiency. The importance of diagnosis of this condition, and differentiation from optic neuritis, lies in its potential reversibility with Vitamin B12 replacement if commenced early.

24. Multiple cranial mononeuropathy secondary to adecarcinoma in a young patient

Author: Dr JM Celi Celi et al

Introduction:

Multiple cranial neuropathy is the asynchronous involvement of several cranial nerves (CN). CN dysfunction may be secondary to injury in any site along its course from the brainstem to superficial soft tissues; the causes of this dysfunction include infectious, inflammatory and neoplastic pathologies, the last are the most frequent etiology.

Clinical case:

36-year-old male patient who consult by peripheral facial paralysis (PFP) and history of facial pain in the right mandible that led to the extraction of the third molar in the previous three months. Physical examination: hypoesthesia in the right trigeminal mandibular branch (V3), atrophy and weakness in right masseter muscle and grade IV H-B right PFP.

Brain MRI: Tumoral lesion in neck’s cervical spaces that affects masticatory space (medial and lateral pterygoid muscle, temporal muscle and masseter muscle), lateropharyngeal space, and deep parotid space; and intracranially in middle cranial fossa, it extends through Meckel’s cavum (MC) and displaces preganglionic trigeminal CN. Right trigeminal nerve incisional biopsy: infiltration by adenocarcinoma with an immunohistochemical profile suggestive of a primary salivary gland tumor.

Figure 1: RMIT1 contrast: tumoral lesion in the masticatory space and deep parotid space

Conclusion:

Author concluded that V3 and VII PC dysfunction in this case is secondary to peripheral involvement due to an infiltrative lesion in neck’s cervical spaces that reaches CM and parotid space.

25. The great mimic: An elusive diagnosis for a multiple cranial polyneuropathy

Author: Dr Tiago Oliveira et al, Neurology Department, Centro Hospitalar, Portugal

Introduction

Sarcoidosis is an immune mediated, inflammatory multisystemic disorder against and unknown antigen, characterized by the presence of non-caseating epithellold granulomas in the absence of an infection.’ Neurological involvement (5-10% of sarcoidosis cases) usually presents with secondary infiltration of multiple cranial nerves. We hereby present a case of and additive cranial polyneuropathy secondary to sarcoidosis.’

Case report

» 53 years female

» Essential benign hypertension

» Bilateral carpal tunnel syndrome

Work-up

2 weeks

3 weeks

Insidious right temporal stabbing headache

Horizontal double vision with right eye abduction palsy

Right peripheral facial palsy with queratitis

» Blood analysis: Slightly increased ESR, speckled ANA (1:160). enzyme. Negative for infectious diseases. Normal CSF analysis:

» Imaging studies: Normal brain and neck MRI; Normal thoracic CT-scan with no mediastinal lymphadenopathy

» Treatment: 7 day course of high dose corticosteroids with slight improvement, followed by oral prednisolone, with full recovery of symptoms.

Image 1: PET Scan Showing right axillary node activation

Image 2: PET Scan Showing right axillary node activation

Conclusion

Author described a case in which a rare diagnosis was made only because of a complete aetiological study in the absence of a clear clinical suspicion. This highlights the need of extensive workup in multiple cranial neuropathies, not only because of their sometimes elusive nature, but also to avoid misdiagnosis and promptly start correct treatment.

26. Celiac disease and peripheral neuropathy: identifying pleiotropic SNPs among established genetic risk variants

Author: Zis P et al, Department of Neurology, medical School, University of Cyprus, Nicosia, Cyprus

Introduction

Celiac disease (CD) is associated with an increased risk of peripheral neuropathy (PN). Whether a genetic component plays a role remains unknown.

Aim:

To detect pleiotropic genetic risk factors among single nucleotide polymorphisms (SNPs) that are associated with CD and PN.

Methods

All CD-associated SNPs were retrieved from the GWAS Catalog and were treated as a SNP network. In order to detect SNP subgroups of this network significantly associated with neuropathic traits, further SNP set enrichment analyses (SNPSEA) were performed via GeneTrail. For this purpose, Phenome-wide Association Studies (PheWAS) were inquired through the Genetrail’s pipeline. Such traits were considered enriched when the false discovery rate (FDR) of each trait-SNP subset (FDR) was <0.05.

Results

Search in the GWAS Catalog returned 251 SNPs across 28 studies that were associated with CD. SNPSEA revealed that 13 SNPs mapped to 10 genes (ETS1, PLEK, DLEU1, FRMD4B, SH2B3, MMEL1, ATXN2, IL12A-AS1, WNT3, ICOSLG), 2 intergenic regions and the RN7SKP226 pseudogene significantly enriched the phenotypic traits “pain in limb”, “inflammatory and toxic neuropathy” and “Type 1 diabetic neuropathy”.

Discussion

Using a GWAS-PheWAS approach author identified 14 pleiotropic genetic risk factors between CD and neuropathic traits. Study findings suggest that a genetic component may predispose for the development of PN in CD patients. Targeted GWAS of CD patients with PN are needed to confirm such predisposition.

27. Descriptive Analysis of Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in the Northern Area of Tenerife

Author: Gonzalez Toledo et al Aim

To describe the basic epidemiological and clinical aspects of CIDP in study Hospital.

Methods

Authors retrospectively reviewed the medical history of all the patients with diagnosis of CIDP in follow-up by Neuromuscular diseases unit between 2012-2021 and performed a descriptive analysis of their main epidemiological and clinical aspects.

Results

» 15 cases of CIDP were found. 11 patients (73%) were males and mean age at diagnosis was 58 years old. Current prevalence is 3.8/100000 people.

» Most frequent first symptoms were isolated paresthesias (33%), pain (20%) or weakness (27%).

» All patients excepting pure sensory CIDP developed motor and sensory symptoms.

Cerebrospinal fluid analysis: all patients had hyperproteinorrachia (>50 mg/dL) and normal leukocyte counts (<10 leukocytes/mm3).

Anti-ganglioside antibodies were negative in all patients excepting a patient who was anti-GQ1b IgM +. Antibodies to neurofascin-155 (Nfasc155), contactin-1 (CNTN1), and contactin-associated protein 1 (Casprl) were tested in 3 refractory-CIDP patients, but were negative. 1 patient died after a respiratory infection.

Conclusion

Author reported that, in the best of their knowledge, it is the first epidemiological and clinical data about CIDP in the Canary Islands. Their results globally agree on those reported in other regions of the world.

28. A case series on a rare diagnosis: Idiopathic Painful Nervus Intermedius Neuropathy

Author: M Yousaf et al

Introduction

Idiopathic painful nervus intermedius neuropathy (IPNIN) is a rare craniofacial pain disorder of unknown etiology presented as continuous or near-continuous pain, with or without superimposed brief paroxysms in the distribution of nervus intermedius. The “nervus intermedius of Wrisberg” is the sensory and parasympathetic division of the facial nerve.

Methods

Electronic charts of patients were reviewed.

Results

Two females, 46 and 63 years old, presented with continuous, 7-9/10 intensity, dull, left deep ear pain with superimposed 7-8 paroxysms of worsening sharp pain per day for 6 months and 6 years, respectively. No other associated symptoms were reported. The 46-year-old patient had no long-term relief with carbamazepine, amitriptyline, and lamotrigine trials, while the 63-year-old patient had failed meloxicam mono-therapy. Both patients were negative for co-relating infections, and magnetic resonance imaging (MR I) of the brain and internal auditory canals did not show any vascular or compressive cause for their pain. Patients were diagnosed with idiopathic painful nervus intermedius neuropathy (ICHD-3/13.3.2.4) after extensive imaging and clinical exams by otolaryngology, neurology, and ophthalmology. The 46-year-old female was started on duloxetine 60 mg daily, and the 63-year-old female has prescribed gabapentin 400 mg twice a day and meloxicam 7.5 mg daily. Within a month, these treatment regimens significantly reduced pain severity and duration for both patients.

Conclusions

IPNIN is a challenging clinical diagnosis established after excluding other pain syndromes within the exact neuroanatomical location. With no standard therapeutic and diagnostic guidelines for IPNIN management, author wanted to highlight excellent results with meloxicam with gabapentin and duloxetine mono-therapy.

29. Electrodiagnosis of ulnar neuropathy at the elbow

Author: Y Abida et al.

Introduction

Electrodiagnosis of ulnar neuropathy at the elbow (UNE) is challenging. Ulnar motor response recoded from abductor digiti minimi (ADM) is insufficient. Extended neurophysiological study is needed to increase the sensitivity of the electroneuromyography.

Aim: To identify neurophysiological findings required to carry the diagnosis of UNE with least risk of error. Methods

Retrospective study including patients with clinical symptoms of UNE. Ulnar motor responses were assessed using three methods 4 Recording from: 1- ADM, 2- First dorsal interosseous (FDI), 3- Flexor carpis ulnaris (FCC). Distal ulnar sensory potential and needle electromyography (EMG) of ulnar and non-ulnar innervated muscles were applied.

Discussion

Study showed that UNE was more frequent in men and manifested merely with sensory signs, similarly to previous studies. In line with other studies, in more than half of the cases, aetiology was unknown. Present study showed similar results on motor conduction studies when recording from ADM or FDI. Yet Kothari MJ et al. found that recording from FDI was more sensitive. FCC was less involved in present study patients and this is consistent with previous data showing that abnormalities recorded from FCC branch are more specific. Since ulnar motor responses recorded from ADM only may be insufficient, electrodiagnosis of UNE according to the involvement of the ADM and FDI could be a practical way to enhance sensitivity and specificity. Our study has some limitations. First, it was difficult to gather data since it was a retrospective study. Second, we couldn’t determine sensitivity and specificity due to the lack of false positive and false negative. Finally, other techniques such as “Inching” could be used when all the 3 branches are normal at NCS.

Conclusion

Electrodiagnosis of UNE is easy performed according to involvement of 2 motor branches of ulnar nerve. Motor conduction responses are often impaired in recording from ADM and FDI muscles.

30. Features of Chronic Inflammatory Demyelinating Polyneuropathy in different age groups at disease onset

Author: Roman A Gapeshin

Introduction

Chronic inflammatory demyelinating polyneuropathy (CIDP) is an acquired progressive or relapse-remitting immune-mediated disease of peripheral nervous system. The diagnosis of CIDP reveals on clinical presentation and electrophysiological data due to European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/ PNS) criteria. The EFNS/PNS criteria were developed for use in daily clinical care and in clinical trials. However, misdiagnosis of CIDP is a current problem, because these criteria are too complicated for use in routine practice in non-specialized in neuromuscular diseases centers.

Aim and Methodology: To determine differences in severity of CIDP in patients of different age at disease onset, divided by World Health Organization in 3 groups: young (18-44), middle-aged (45-59), senior (60-74). 112 patients with confirmed CIDP diagnosis were investigated at inpatient department: 26 young-aged patients (average age of CIDP onset — 35.04±1.48 years), 55 middle-aged patients (average age of CIDP onset — 52.47±0.63 years) and 31 senior-aged patients (average age of CIDP onset — 67.52±1.18 years). Distribution by course type and type of CIDP demonstrated in Table 1 and 2. To assess the severity, 3 scales were used: Neuropathy Impairment Scale (NIS), Medical Research Council (MRC) and Inflammatory Neuropathy Cause and Treatment (INCAT) scales. Clinical and laboratory assessment were performed to all patients.

Results

There was significant difference in CIDP severity between age groups. Most severe CIDP affects senior patients, less severe CIDP in young and middle-aged patients. Results obtained by different scales were statistically significantly correlated (p<0.05) (Table 3). Significant differences in laboratory results between age groups weren’t found.

Conclusion

Diagnosis of CIDP is a challenging approach, which consumes a lot of time in comparison with many other neurological diseases. CIDP can affect people at various ages: from childhood to senile age. Present study showed that the severity of CIDP is different also due to age of onset. This data can help to make an additional attention to patients who revealed CIDP at senior and young age