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A 67-year-old man presented with 5 months of worsening memory impairment and sensory gait ataxia on the background of symptomatic anaemia. He experienced falls, agitation and became socially withdrawn over 3 weeks, resulting in hospital admission. On examination, he had sensory gait ataxia consistent with a dorsal column syndrome. He scored 13/30 on the Montreal Cognitive Assessment. Serum analysis showed normocytic anaemia and leucopenia, severe hypocupraemia, reduced caeruloplasmin and normal zinc levels. Overuse of zinc-containing denture cream was the cause of excess zinc ingestion and resultant copper deficiency, leading to blood dyscrasia and myelopathy. The cream was withdrawn and intravenous and then oral copper supplementation was implemented. Direct questions with regard to excess zinc in the diet and serological testing of copper and zinc should be considered in any patient with a dorsal column syndrome, particularly with concurrent anaemia. Copper deficiency may also have a role in exacerbating pre-existing cognitive impairment.

BACKGROUND Neurologic presentations resulting from nitrous oxide (N2 O) abuse are increasing in Australia and worldwide. Despite known neuropsychiatric sequelae nitrous oxide canisters remain readily available and its use unregulated. AIMS To examine the demographics, clinical and electrophysiological findings of patients presenting with neurological complications of N2 O abuse, and thus inform clinicians and public health decision makers of the significant public health concerns of this increasing practice. METHODS Consecutive patients presenting to a tertiary referral, metropolitan hospital were included in this series. Patients were identified by a search of discharge summaries of patients admitted with acute or subacute neuropathy or myelopathy and a history of N2 O abuse, and from the electrophysiology database. RESULTS Thirteen patients were identified, most presenting with subacute paraesthesia, sensory ataxia and lower limb weakness. Eleven had low serum vitamin B12 . Spinal magnetic resonance imaging was consistent with subacute combined degeneration (SACD) in 8. Nerve conduction studies revealed a motor or sensorimotor axonal neuropathy (3 with motor predominance). There was a bimodal demographic distribution consisting of socially isolated, international university students and local residents with a history of mental illness and polydrug abuse. CONCLUSIONS Recreational N2 O use is an emerging health problem in Australia. International university students and patients with pre-existing mental illness or polydrug use appear to be at increased risk. A severe motor neuropathy may emerge following Vitamin B12 replacement. Public health measures are required to limit the availability of N2 O and to educate adolescents and young adults about the potential for significant harm. This article is protected by copyright. All rights reserved.

Background and ObjectiveMultiple studies highlighting the diagnostic utility of neurofascin-155 (NF155)–immunoglobulin G4 (IgG4) in chronic demyelinating inflammatory polyradiculoneuropathy (CIDP) have been published. However, few studies comprehensively address the long-term outcomes or clinical utility of NF155–immunoglobulin M (IgM) or NF155–immunoglobulin G (IgG) in the absence of NF155-IgG4. We evaluated phenotypic and histopathologic specificity and differences in outcomes between these NF155 antibody isotypes or IgG subclasses. We also compare NF155-IgG4-seropositive cases to other seropositive demyelinating neuropathies.MethodsNeuropathy patient sera at Mayo Clinic were tested for NF155-IgG4, NF155-IgG, and NF155-IgM autoantibodies. Demographic and clinical data of all seropositive cases were reviewed.ResultsWe identified 32 NF155 cases (25 NF155-IgG-positive [20 NF155-IgG4-positive], 7 NF155-IgM-seropositive). NF155-IgG4-seropositive patients clinically presented with distal more than proximal muscle weakness, positive sensory symptoms (prickling, asymmetric paresthesia, neuropathic pain), and gait ataxia. Cranial nerve involvement (11/20 [55%]) and papilledema (4/12 [33%]) occurred in many. Electrodiagnostic testing (EDX) demonstrated demyelinating polyradiculoneuropathy (19/20 [95%]). Autonomic involvement occurred in 45% (n = 9, median composite autonomic scoring scale score 3.5, range 1–7). Nerve biopsies from the NF155-IgG4 patients (n = 11) demonstrated grouped segmental demyelination (50%), myelin reduplication (45%), and paranodal swellings (50%). Most patients needed second- and third-line immunosuppression but had favorable long-term outcomes (n = 18). Among 14 patients with serial EDX over 2 years, all except one demonstrated improvement after treatment. NF155-IgG-positive, NF155-IgG4-negative (NF155-IgG-positive) and NF155-IgM-positive patients were phenotypically different from NF155-IgG4-seropositive patients. Sensory ataxia, neuropathic pain, cerebellar dysfunction, and root/plexus MRI abnormalities were significantly more common in NF155-IgG4-positive compared to myelin-associated glycoprotein (MAG)–IgM neuropathy. Chronic immune sensory polyradiculopathy (CISP)/CISP-plus phenotype was more common among contactin-1 neuropathies compared to NF155-IgG4-positive cases. NF155-IgG4-positive cases responded favorably to immunotherapy compared to MAG-IgM-seropositive cases with distal acquired demyelinating symmetric neuropathy (p < 0.001) and had better long-term clinical outcomes compared to contactin-1 IgG (p = 0.04).DiscussionWe report long-term follow-up and clinical outcome of NF155-IgG4 cases. NF155-IgG4 but not IgM or IgG cases have unique clinical–electrodiagnostic signature. We demonstrate NF155-IgG4-positive patients, unlike classical CIDP with neuropathic pain and dysautonomia common at presentation. Long-term outcomes were favorable.Classification of EvidenceThis study provides Class III evidence that NF155-IgG4-seropositive patients, compared to patients with typical CIDP, present with distal more than proximal muscle weakness, positive sensory symptoms, and gait ataxia.

BACKGROUND: Although hereditary ataxias are a group of clinically and genetically heterogeneous disorders, specific clinical clues can sometimes incriminate certain genes. This can trigger genetic testing in sporadic patients or prompt dissecting certain genes more thoroughly when initial genetic testing is negative. Also for the assembly of gene panels and interpretation of the results, genotype-phenotype correlations remain important to establish. METHODS: We clinically evaluated a Belgian family with autosomal dominant inherited sensory ataxia and variable pyramidal involvement and performed targeted clinical exome sequencing. Secondly, we retrospectively screened sequencing data of an in-house cohort of 404 patients with neuromuscular disorders for variants in the identified gene RNF170. RESULTS: All affected family members showed sensory ataxia on examination. Pyramidal involvement, and sometimes slow-pursuit abnormalities and/or a sensory neuropathy, were more variable findings. We identified the heterozygous variant p.Arg199Cys in RNF170 in all three affected siblings of our family. We did not find additional pathogenic variants in RNF170 in our in-house neuromuscular cohort. CONCLUSIONS: We confirm the heterozygous variant p.Arg199Cys in RNF170 in a Belgian family with autosomal dominant sensory ataxia and variable pyramidal involvement. This constitutes a rare but clinically recognizable phenotype that warrants testing of RNF170. Unlike the distinctive bi-allelic loss of function variants in RNF170 associated with hereditary spastic paraplegia (HSP), the p.Arg199Cys variant is the only one reported in sensory ataxia. It is important for neurologists to be aware of this characteristic phenotype and to include this gene in gene panels for ataxia and HSP. ispartof: EUROPEAN JOURNAL OF NEUROLOGY vol:29 issue:1 pages:345-349 ispartof: location:England status: published

BACKGROUND AND PURPOSE Nitrous oxide misuse is a recognized issue worldwide. Prolonged misuse inactivates vitamin B12, causing a myeloneuropathy. METHODS Twenty patients presenting between 2016 and 2020 to tertiary hospitals in Sydney with myeloneuropathy due to nitrous oxide misuse were reviewed. RESULTS The average age was 24 years, and mean canister consumption was 148 per day for 9 months. At presentation, paresthesias and gait unsteadiness were common, and seven patients were bedbound. Mean serum B12 was normal (258 pmol/L, normal range [NR] = 140-750) as was active B12 (87 pmol/L, normal > 35). In contrast, mean serum homocysteine was high (51 μmol/L, NR = 5-15). Spinal magnetic resonance imaging (MRI) showed characteristic dorsal column T2 hyperintensities in all 20 patients. Nerve conduction studies showed a predominantly axonal sensorimotor neuropathy (n = 5). Patients were treated with intramuscular vitamin B12, with variable functional recovery. Three of the seven patients who were bedbound at presentation were able to walk again with an aid at discharge. Of eight patients with follow-up data, most had persistent paresthesias and/or sensory ataxia. Mobility scores at admission and discharge were not significantly correlated with the serum total and active B12 levels or cumulative nitrous oxide use. There were no significant trends between serum active B12 level and cumulative nitrous oxide use (Spearman rho = -0.331, p = 0.195). CONCLUSIONS Nitrous oxide misuse can cause a severe but potentially reversible subacute myeloneuropathy. Serum and active B12 can be normal, while elevated homocysteine and dorsal column high T2 signal on MRI strongly suggest the diagnosis. Neurological deficits can improve with abstinence and B12 supplementation, even in the most severely affected patients.

Mutations in Myelin Protein Zero (MPZ) cause CMT1B, the second leading cause of CMT1. Many of the >200 mutations cause neuropathy through a toxic gain of function by the mutant protein such as ER retention, activation of the Unfolded Protein Response (UPR) or disruption of myelin compaction. While there is extensive literature on the loss of function consequences of MPZ in heterozygous Mpz +/- null mice, there is little known of the consequences of MPZ haploinsufficiency in humans. We identified six patients from different families with p.Tyr68Ter or p.Asp104fs heterozygous mutations of MPZ that are predicted to cause a premature termination and nonsense mediated decay of the mutant allele. Five patients were evaluated in Milan and one in Iowa City; all should be haploinsufficient for MPZ. Patients were evaluated clinically and by electrophysiology. Sensory ataxia dominated the clinical presentation with only mild weakness present in five of the six patients. Symptoms presented in adulthood in all patients and only one individual had a CMTNSv2 >5. Deep tendon reflexes were absent in all patients. Patients with likely MPZ loss of function due to mutations that cause haplodeficiency in MPZ have a mild, predominantly large fiber sensory neuropathy that serves as a human equivalent to the neuropathy observed in heterozygous Mpz null mice. Successful therapeutic approaches in treating Mpz deficient mice may be candidates for trials in these and similar patients.

AP3B2 is one of the subunits of vesicle coat protein AP3 and is specifically expressed in central nervous system neurons. AP3B2 antibody has been reported in patients with autoimmune cerebellar ataxia and various extracerebellar symptoms. However, there have been few reports on its clinical features and treatment response. We report a 47-year-old man with AP3B2 antibody who presented with insidious-onset paresthesia and gait disturbance. His serum and cerebrospinal fluid (CSF) showed reactivity with the cytoplasm of Purkinje cells and granular layer synapses comparable to the reported specific pattern of anti-AP3B2 IgG, and this was confirmed by a cell-based assay. His symptoms improved after the administration of intravenous immunoglobulin, and oral prednisone and mycophenolate mofetil. Extensive examination and long-term follow-up showed no evidence of malignancy. A literature review was included to emphasize the neurological syndrome associated with this rare autoantibody. Eleven cases with AP3B2 antibody, including our patient, were identified. The diversity of symptoms, including cerebellar and sensory ataxia, paresthesia, and weakness, was in line with the extensive binding of AP3B2 antibody to the spinal cord gray matter, dorsal root ganglia, cerebellar cortex, and nucleus. In the CSF, half of patients had elevated white blood cell counts, increased protein concentrations, or CSF-specific oligoclonal bands. All previous cases had subacute onsets and no improvement was noted after immunotherapy. Our case indicated that disorders associated with AP3B2 antibody can also start insidiously. Immunotherapy is warranted given the possibility of clinical improvement.

Summary Background Vitamin B12 deficiency has been associated with a very wide spectrum of neurologic manifestations and the majority of cases occur in infants, pregnant women, and elderly people. In children, common neurological complications include neuropathy, neuropsychiatric features, infantile tremor syndrome, developmental delay, cognitive decline, spastic paraparesis due to subacute combined degeneration of cord, seizures, encephalopathy, extrapyramidal features, and neuropathy. Vitamin B12 is known to cause sensory ataxia, along with impaired position and vibration sense, as well as variable spasticity, as a part of subacute combined degeneration of the spinal cord. However, only a few cases of isolated cerebellar ataxia caused by vitamin B12 deficiency have been reported in published literature. Methods and results We are reporting a case of isolated cerebellar ataxia progressing over months in a 13-year-old boy. He also had associated knuckle hyperpigmentation, megaloblastic anemia and his magnetic resonance imaging of the brain was normal. Complete blood count showed hemoglobin of 8.6 gm/dl and peripheral smear showed macrovalocytes and few hypersegmented neutrophils. Serum vitamin B12 level was low (134 pg/mL). He was started on daily intramuscular vitamin B12 supplementation and he showed a favorable response after the first week. Conclusions Clinicians need to consider vitamin B12 deficiency as one of the rare etiological possibilities in children presenting with isolated subacute onset/chronic ataxia, as supplementation of this vitamin is likely to cause a complete reversal of ataxia in such children.

The aim was to analyze the contemporary scientific literature on Devic’s opticomyelitis and to present a case report from our clinical practice. Based on the patient’s complaints, case history and features of clinical course, objective neurological status, clinical laboratory and additional examination methods, characteristic MR-patterns, consultations of related specialists and differential diagnostics, we made the clinical diagnosis according to ICD-10: G36.0 Devic’s opticomyelitis, exacerbation, with a sustained bilateral lesion of the optic nerves in the form of retrobulbar neuritis with the development of partial atrophy of the optic nerves in both eyes, spinal cord lesions with common cystic, cicatrical and atrophic alterations at C1-Th8 level with moderate lower paraparesis, expressed by sensory ataxia, sensory disturbances by the descending conductive type from Th10, impaired function of pelvic organs by the type of acute urinary retention, asthenic and neurotic syndrome. Widespread cases of demyelinating pathology in medical practice and complexity of differential diagnostics determine the need for a specific diagnostic algorithm. This algorithm should consider anamnestic data along with the course of the disease, clinical, laboratory and instrumental examination, including neuroimaging, analysis of CSF for oligoclonal bands, analysis for IgG antibodies to AQP4, which will allow to carry out diagnostics and to decide on tactics for further management of patients of this cohort. Further research is needed to conduct additional studies for optimization of tactics for dynamics monitoring and improvement of diagnostic, treatment and rehabilitation measures in patients with Devic’s opticomyelitis, including appropriate immunological control, given the complexity of differential diagnostics and the affinity of this pathology to multiple sclerosis.

ObjectiveTo test the hypothesis that myeloneuropathy is a presenting phenotype of paraneoplastic neurologic syndromes we retrospectively reviewed clinical, radiologic, and serologic features of 32 patients with concomitant paraneoplastic spinal cord and peripheral nervous system involvement.MethodsObservational study investigating patients with myeloneuropathy and underlying cancer or onconeural antibody seropositivity.ResultsAmong 32 patients with paraneoplastic myeloneuropathy, 20 (63%) were women with median age 61 years (range 27–84 years). Twenty-six patients (81%) had classified onconeural antibodies (amphiphysin, n = 8; antineuronal nuclear antibody [ANNA] type 1 [anti-Hu], n = 5; collapsin response mediator protein 5 [CRMP5] [anti-CV2], n = 6; Purkinje cell cytoplasmic antibody type 1 [PCA1] [anti-Yo], n = 1; Purkinje cell cytoplasmic antibody type 2 [PCA2], n = 2; kelch-like protein 11 [KLHL11], n = 1; and combinations thereof: ANNA1/CRMP5, n = 1; ANNA1/amphiphysin, n = 1; ANNA3/CRMP5, n = 1). Cancer was confirmed in 25 cases (onconeural antibodies, n = 19; unclassified antibodies, n = 3; no antibodies, n = 3). Paraneoplastic myeloneuropathies had asymmetric paresthesias (84%), neuropathic pain (78%), subacute onset (72%), sensory ataxia (69%), bladder dysfunction (69%), and unintentional weight loss >15 pounds (63%). Neurologic examination demonstrated concomitant distal or asymmetric hyporeflexia and hyperreflexia (81%), impaired vibration and proprioception (69%), Babinski response (68%), and asymmetric weakness (66%). MRI showed longitudinally extensive (45%), tract-specific spinal cord T2 hyperintensities (39%) and lumbar nerve root enhancement (38%). Ten of 28 (36%) were unable to ambulate independently at last follow-up (median 24 months, range 5–133 months). Combined oncologic and immunologic therapy had more favorable modified Rankin Scale scores at post-treatment follow-up compared to those receiving either oncologic or immunologic therapy alone (2 [range 1–4] vs 4 [range 2–6], p < 0.001).ConclusionsParaneoplastic etiologies should be considered in the evaluation of subacute myeloneuropathies. Recognition of key characteristics of paraneoplastic myeloneuropathy may facilitate early tumor diagnosis and initiation of immunosuppressive treatment.

The pure sensory variant of Guillain-Barre syndrome "GBS" is controversial. Scarce case reports in the literature have described pure sensory presentations secondary to acute demyelination of peripheral sensory nerves. Pure sensory GBS secondary to axonal damage is rarer and even more controversial owing to a significant overlap with sensory neuronopathy. A 31-year-old lady with history of a recent primary varicella zoster virus (VZV) infection presented with acute onset of sensory symptoms and signs involving her four limbs and the trunk, without weakness. Examination was remarkable for severe impairment in all sensory modalities in her limbs and trunk, pseudo-athetoid limb movements, sensory ataxia, positive Romberg's sign, and areflexia, with no motor involvement. CSF analysis showed elevated protein without pleocytosis known as albuminocytological dissociation. MRI of the spine with contrast showed multiple root enhancement. Nerve conduction studies "NCS" demonstrated absent sensory action potentials, with normal motor nerves responses. Initial electromyography was normal. After differential diagnoses were appropriately excluded, the patient was diagnosed with pure sensory axonal GBS and treated with IVIG for five days. Gradual clinical improvement was seen over the following months, with improvement in six-month GBS disability score down to two. Follow-up NCS showed findings similar to the initial study but follow-up EMG studies revealed denervation potentials in multiple levels, suggesting a subclinical axonal motor involvement and excluding sensory neuronopathy. To our best knowledge, this case represents the first case of pure sensory GBS with onset after a documented primary VZV infection. The findings in this case illustrate the difficulties in diagnosing pure sensory GBS and the significance of an early treatment. It also demonstrates the potential value of follow-up EMGs in excluding sensory neuronopathy as an important differential diagnosis for this condition.

Introduction Chronic immune polyradiculopathies (sensory, motor, and mixed) are uncommon. Methods In this single-center, retrospective study, the inclusion criteria for participants were progressive sensory ataxia and/or areflexic limb weakness; tibial somatosensory evoked potential (SSEP) abnormalities of the N22 and P40 potentials with normal sensory and motor nerve conduction studies or root involvement, according to magnetic resonance imaging (MRI); and albuminocytological dissociation. Results Eight patients were included in our study. Two had weakness, two had sensory ataxia, and four had both weakness and ataxia. Patients with weakness had abnormal SSEPs and patients with sensory ataxia also had absent F waves. Electromyography showed chronic denervation. MRI scans confirmed thickening and enhancement of roots. The patients responded to corticosteroid treatment. Discussion The overlapping clinicoelectrophysiological findings and similarities in radiological and therapeutic responses suggest that these entities are clinical variants of the same disease. The terms CIS(m)P, CI(s)MP, and CISMP (for chronic immune sensory motor polyradiculopathy) could be used to denote the predominant clinical involvement.

A 57-year-old woman presented with progressive ataxia and falls. She was in her usual state of health until she developed sudden onset of progressive imbalance for a month. She then presented to an emergency department. Examination revealed significant vibration sensation impairment and proprioceptive loss, with normal pinprick and temperature sensation; sensory ataxia with pseudoathetosis in the hands; no finger to nose incoordination; normal rapid alternating movements of upper extremities; heel to shin incoordination; diminished deep tendon reflexes; wide-based gait; and positive Romberg test. She did not have cognitive impairment, nystagmus, dysarthria, weakness, muscle atrophy, or fasciculations.

In its typical presentation, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) occurs more often in old males as a progressive/recurrent motor and sensory nerve dysfunction with tendon areflexia. However, CIDP has also atypical clinical presentations, including pure sensory neuropathies, among which chronic immune sensory polyradiculopathy (CISP) accounts for only 0.5% of all CIDP, with no juvenile cases reported as yet. A 17-year-old girl presented for a progressive sensory ataxia and hands clumsiness. Diffuse tendon areflexia and hypokinaesthesia were observed. Motor and sensory nerve conduction studies were normal. F-waves were normal in median nerves and elongated in tibial nerves. H-reflex and somatosensory evoked potentials (SSEP) were absent. CSF normal cellularity with hyperproteinorrachia was found. Paraneoplastic, metabolic, and paraproteinemic neuropathies were excluded. A diagnosis of CISP has been made based on the presence of pure sensory symptoms in a polyneuropathic distribution, normal peripheral nerve conduction studies, and two supportive criteria (SSEP and CSF). Our paper describes the first CISP case in the pediatric age. We confirm SSEP and CSF as useful complementary tests for this diagnosis also at this age and suggest that clinicians should consider CISP in the spectrum of sporadic sensory ataxias of the pediatric age. We also suggest that in the presence of normal F-wave and peripheral motor nerve conduction, an absent H-reflex can further substantiate SSEPs in the diagnosis of CISP. Intravenous immunoglobulins were rapidly effective and safe.

Background and purpose Neurological manifestations have been identified in the context of autoimmune hepatitis (AIH). Previous case reports highlighted the association between AIH and sensory neuronopathy (SN). Despite that, little is known about the frequency of AIH-related SN and its clinical/neurophysiological profile. Moreover, it is not clear whether SN is an AIH-specific manifestation or related to chronic liver damage. Methods Seventy consecutive AIH patients were enrolled and their characteristics were compared with 52 consecutive patients with chronic active hepatitis B. All subjects underwent clinical and neurophysiological evaluation. Further comparisons were performed between AIH SN and AIH non-SN patients. Results Mean ages and male:female proportions in the AIH and chronic active hepatitis B groups were 42.2 ± 16.3/51.7 ± 13.6 years and 14:56/29:23, respectively. The frequencies of carpal tunnel syndrome, radiculopathy and polyneuropathy were similar between groups. In contrast, SN was identified only in AIH patients (5/70 vs. 0/52, P = 0.04); the overall prevalence of AIH-related SN was 7% with an average profile of a woman in her 40s with asymmetric onset of sensory deficits that chronically evolved to disabling proprioceptive ataxia associated with marked dysautonomia. Neurological disability and hepatocellular damage did not follow in parallel. Anti-fibroblast growth factor receptor type 3 antibodies were found in 3/5 (60%) of the patients with AIH-related SN. Clinical or demographic predictors of SN in the context of AIH could not be identified. Conclusion Sensory neuronopathy, but not other peripheral nervous system diseases, is a specific AIH neurological manifestation. It is often disabling and, in contrast to hepatocellular injury, does not respond to immunosuppression.

Peripheral myelin protein 22 (PMP22) related neuropathies account for over 50% of inherited peripheral neuropathies. A gene copy variation results in CMT1A (duplication) and hereditary neuropathy with liability to pressure palsies (HNPP; single deletion). Point mutations comprise both phenotypes. The underlying pathological mechanisms are incompletely understood and biallelic mutations of PMP22 are very rare. We describe a 9-year-old girl who presented before the age of 1 year with severe locomotor delay. She now requires support for standing and walking in view of her severe sensory ataxia. Strikingly, her muscle power and bulk are close to normal in all segments. Nerve conduction studies showed sensory-motor velocities below 5 m/s. Genetic analysis revealed a homozygous sequence change in the PMP22 gene causing the loss of termination codon (c.483A > G; p.[*161Trpext*10]), extending the protein by 9 amino acids. Both heterozygous parents have neurophysiological abnormalities consistent with HNPP, consistent with this being a loss-of-function mutation. PMP22-deficient human models are rare but important to decipher the physiological function of the PMP22 protein in vivo. The predominance of large fiber sensory involvement in this and other rare similar cases suggests a pivotal role played by PMP22 in the embryogenesis of dorsal root ganglia in humans.

Background Primary orthostatic tremor (OT) is a rare movement disorder characterized by a 13–18 Hz leg tremor, which arises when standing and is relieved by walking/sitting. Those affected generally do not fall, but experience fear of falling, lessened by ambulation. Because of its low amplitude, the tremor is not readily visible, and diagnosis requires confirmation with surface electromyography (sEMG). Recently, applications using the accelerometer feature of smartphones have been used to detect and quantify tremors, including OT, though the accuracy of smartphone accelerometry (SPA) in diagnosing OT is unknown. Methods We completed SPA in consecutive adults (18+ years), who presented to our neurology clinic with either subjective leg shakiness upon standing or unsteadiness when standing that lessened with ambulation, which comprised 59 of 2578 patients. We assessed tremor using the StudyMyTremor application on an iPhone 6 s adhered with tape to the patient’s tibialis anterior. Surface electromyography was completed on the same muscle. The primary outcome of this study was to determine SPA’s sensitivity and specificity in detecting OT compared with surface electromyography. Results Fifty-nine patients with the following diagnoses were included: OT (6), Parkinson’s disease, Hereditary Spastic Paraplegia, orthostatic hypotension, essential tremor, spinal cerebellar ataxia, sensory ataxia and functional movement disorder. Smartphone accelerometry detected a 13–18 Hz tremor in 5 of 6 patients diagnosed with OT by sEMG with no false positives in other conditions, yielding a sensitivity of 83%, specificity of 100% in the cohort we studied. Conclusions Though a larger sample size is desirable, preliminary data suggest that smartphone accelerometry is an alternative to surface electromyography in diagnosing OT.

The development of autoimmune antibody panels has improved the diagnosis of paraneoplastic neurological disorders (PNDs) of the brain and spinal cord. Here, we present a case of a woman with a history of breast cancer who presented with a subacute sensory ataxia that progressed over 18 months. Her examination and diagnostic studies were consistent with a myelopathy. Metabolic, infectious, and autoimmune testing were non-diagnostic. However, she responded to empirical immunosuppression, prompting further workup for an autoimmune etiology. An unbiased autoantibody screen utilizing phage display immunoprecipitation sequencing (PhIP-Seq) identified antibodies to the anti-Yo antigens cerebellar degeneration related protein 2 like (CDR2L) and CDR2, which were subsequently validated by immunoblot and cell-based overexpression assays. Furthermore, CDR2L protein expression was restricted to HER2 expressing tumor cells in the patient's breast tissue. Recent evidence suggests that CDR2L is likely the primary antigen in anti-Yo paraneoplastic cerebellar degeneration, but anti-Yo myelopathy is poorly characterized. By immunostaining, we detected neuronal CDR2L protein expression in the murine and human spinal cord. This case demonstrates the diagnostic utility of unbiased assays in patients with suspected PNDs, supports prior observations that anti-Yo PND can be associated with isolated myelopathy, and implicates CDR2L as a potential antigen in the spinal cord.

Chronic immune sensory polyradiculopathy (CISP) is a rare variant of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). We describe a man with isolated sensory ataxia whose initial investigations included normal nerve conduction studies and normal non-enhanced MR imaging of whole spine, but whose subsequent investigations showed delayed somatosensory evoked potential (SSEP) responses of the lower limbs, elevated cerebrospinal fluid (CSF) protein and lumbosacral nerve roots enhancement on MR imaging. We diagnosed CISP and he improved following intravenous immunoglobulin. Proposed diagnostic criteria for CISP are sensory symptoms with a polyneuropathic distribution without weakness, and normal motor and sensory nerve conduction and electromyography (EMG) studies, plus at least two of: abnormal SSEPs not due to central nervous system (CNS) involvement, MRI showing gadolinium enhancement or hypertrophy of the nerve roots, cauda equina or plexuses, and elevated CSF protein with normal cell count. Intravenous immunoglobulin is an effective treatment.

The peripheral nerve is usually spared in chronic immune sensory polyradiculoneuropathy (CISP) according to a literature review; however, an extended-spectrum of CISP, CISP-plus, was introduced recently. Here we report a 29-year-old Taiwanese man who presented with numbness and hypoesthesia in all distal extremities, tightness sensation in the left posterior thigh, and sensory ataxia for three months. The clinical and neurophysiological examinations revealed proximal sensory abnormalities along with sural nerve involvement. The elevated protein level of cerebrospinal fluid (CSF) was noted and enlarged dorsal root ganglia were seen on the magnetic resonance imaging (MRI) of the whole spine. Autoimmune workup showed only positive human leukocyte antigen (HLA)-B27. Biopsy of the sural nerve revealed inflammatory demyelinating neuropathy. Only mild improvement was noted after methylprednisolone pulse therapy (1,000mg/day) for three days, and he was then treated with intravenous immunoglobulin with the dosage of 2g/kg-BW followed by azathioprine, and objective improvements were reported. Different from the previous case reports, CISP may also associate with peripheral nerve involvements. A sural nerve biopsy could assist the diagnosis. Further investigation is needed for the possible immune association between CISP-plus and HLA-B27.

We report clinical and detailed nerve conduction findings in case of polyneuropathy associated with kappa light chains monoclonal gammopathy of undetermined significance with progression to lymphoproliferative disorder. A 55-year-old man had a predominantly distal, chronic (5 years duration), slowly progressive, symmetric, predominantly sensory impairment with sensory ataxia, and mild weakness. M protein was identified by serum protein electrophoresis. The kappa/lambda ratio of free light chains was significantly elevated to 11.96. The cerebrospinal fluid protein level was elevated at 3.5 g/L. This case study has revealed 2 unusual electrophysiological phenomena-a very unusual prolongation of distal motor latencies of compound muscle action potentials (CMAP) up to 86.5 ms and impaired excitability of the distal segments of the peripheral nerves. The distal CMAP areas were considerably lower compared with the proximal CMAP areas. Radiography of the skull revealed osteolytic lesions.

BackgroundThe concurrence of anti-contactin 1 (CNTN1) antibody-associated chronic inflammatory demyelinating polyneuropathy (CIDP) and membranous nephropathy (MN) has previously been reported in the literature. CIDP with autoantibodies against paranodal proteins are defined as autoimmune nodopathies (AN) in the latest research. In view of the unclear relationship between CIDP and MN, we performed a case study and literature review to investigate the clinical characteristics of anti-CNTN antibody-associated AN with MN.MethodsWe detected antibodies against NF155, NF186, CNTN1, CNTN2, CASPR1 and PLA2R in blood samples of a patient with clinically manifested MN and concomitant peripheral neuropathyviadouble immunofluorescence staining and conducted a quantitative measurement of anti-PLA2R IgG antibodiesviaenzyme-linked immunosorbent assay (ELISA). Case reports of anti-CNTN1 antibody-associated AN, anti-CNTN1 antibody-associated AN with MN, and CIDP with MN were retrieved through a literature search for a comparative analysis of clinical characteristics. The cases were grouped according to the chronological order of CIDP and MN onset for the comparison of clinical characteristics.ResultsA 57-year-old man with anti-PLA2R positive MN was admitted to the hospital due to limb numbness, weakness, and proprioceptive sensory disorder. He was diagnosed with anti-CNTN1 antibody-associated AN and recovered well after immunotherapy. Our literature search returned 22 cases of CIDP with MN that occurred before, after, or concurrently with CIDP. Good responses were achieved with early single-agent or combination immunotherapy, but eight out of the 22 patients with CIDP and concomitant MN ultimately developed different motor sequelae. Five patients had anti-CNTN1 antibody-associated AN with MN. Among these patients, males accounted for the majority of cases (male:female=4:1), the mean age at onset was late (60.2 ± 15.7 years, range 43–78 years), and 40% had acute to subacute onset. Clinical manifestations included sensory-motor neuropathy, sensory ataxia caused by proprioceptive impairment, and elevated cerebrospinal fluid protein levels.ConclusionThe age at onset of CIDP with MN was earlier than that of anti-CNTN1 antibody-associated AN. MN may occur before, after or concurrently with CIDP. The early detection and isotyping of anti-CNTN1 and anti-PLA2R antibodies and the monitoring of isotype switching may be essential for suspected CIDP patients.

New and emerging evidence describing the role of autoantibodies to nodal and paranodal proteins in the pathogenesis of chronic inflammatory demyelinating polyneuropathy (CIDP) has arisen over the past decade, with significant diagnostic, therapeutic and prognostic implications. Although rare, CIDP with anti-contactin-1 (CNTN1) IgG4 antibodies has a distinct pathogenesis and clinical phenotype that differs from both typical CIDP and its other atypical variants. Here, we report the case of a young normally well 49-year-old man from rural Australia with severe refractory anti-CNTN1-mediated CIPD who presented like a case of Guillain-Barre syndrome (GBS) who improved dramatically after chemoimmunotherapy with Rituximab and who also had an unexpected late response to subsequent treatments with intravenous immunoglobulin (IVIg). In reporting this case, we hope to highlight important considerations in the diagnosis and treatment of patients with severe refractory CIDP, and especially those patients with anti-CNTN1 seropositive disease. References Vural A, Doppler K, Meini E. Autoantibodies against the node of ranvier in seropositive chronic inflammatory demyelinating polyneuropathy: diagnostic, pathogenic, and therapeutic relevance. Frontiers in Immunology 2018;9:1–14. Miura Y, Devaux JJ, Fukami Y, Manso C, Belghazi M, Wong AHY, et al. Contactin 1 IgG4 associates to chronic inflammatory demyelinating polyneuropathy with sensory ataxia. Brain 2015;138:1484–1491. Bunschoten C, et al. Progress in diagnosis and treatment of chronic inflammatory demyelinating polyradiculoneuropathy. The Lancet Neurology 2019;18(8):784–794. Querol L, Nogales-Gadea G, Rojas-Garcia R, et al. Antibodies to contactin-1 in chronic inflammatory demyelinating polyneuropathy. Annals of Neurology 2013;73:370–380. Querol L, et al. Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins. Neurology, Neuroimmunology & Neuroinflammation 2015;2(5):1–6.

A 20-year-old student presented with progressive swaying while walking, worse in the dark, for 2 weeks. He was a lifelong vegetarian but had no other comorbidities. There was no family history of any neurological illness. On examination, he had grossly impaired vibration and joint position sense in both lower limbs with preserved light touch, pain and temperature sensations. There were no motor or cerebellar deficits and reflexes were normal. Palpation of nerves did not reveal any thickening or nodularity. Blood investigations showed macrocytosis with a mean corpuscular volume of 117 fL, haemoglobin of 146 g/L and moderate eosinophilia (14%). Vitamin B12 levels were low (55 pg/mL) with normal folate levels. Nerve conduction studies were normal. MRI of the brain with whole spine showed T2/fluid-attenuated inversion recovery (FLAIR) hyperintensities in bilateral deep white matter along with T2/FLAIR hyperintensities in the posterolateral region of the thoracic cord which was suggestive of vitamin B12 deficiency (figure 1). Erythrocyte sedimentation rate was 14 mm/first hour. Fasting and postprandial sugar levels as well as glycated haemoglobin level were normal. Fasting …