How long is IVIg effective in multifocal motor neuropathy?

The authors treated 10 patients with multifocal motor neuropathy (MMN) responding to an initial course of IV immunoglobulin (IVIg) with periodic infusion for 5 to 12 years (mean 8.2 years). At last follow-up, only two patients had maintained the maximal improvement achieved during therapy while eight worsened despite increasing Ig dosage. This decline started after 3 to 7 years (mean 4.8 years) of therapy and correlated with a reduction of distal compound muscle action potential amplitudes (p < 0.019). The effectiveness of IVIg in MMN often declines after several years possibly associated with the development of axonal degeneration.     

An open-label trial of rituximab (Rituxan®) in multifocal motor neuropathy

Multifocal motor neuropathy (MMN) is an acquired demyelinating motor neuropathy. Intravenous immunoglobulin (IVIg) has been found to be safe and effective. Rituximab, a genetically engineered monoclonal antibody against CD-20 antigen, has been reported effective in immune disorders including MMN. We performed an open-label trial to determine if rituximab would reduce the IVIg requirement, disability, and impairment, and be safe in patients with MMN. Six MMN patients, who were on periodic IVIg treatments, received two doses of IV rituximab (1,000 mg) given 2 weeks later. Assessments were performed at baseline and at 2, 4, 6, 8, 10, and 12 months. The primary outcome was total amount of IVIg used during the 12-month study compared to the 12 months prior. Secondary outcomes included changes in Medical Research Council (MRC) sum scores, grip strength, disability and handicap scores, and safety. There was no significant change in IVIg use, MRC sum score, grip strength, overall disability sum score, or Rotterdam handicap scale. One patient developed a hypersensitivity reaction during the first infusion that responded to adjustments in the infusion rate and treatment with diphenhydramine and acetaminophen. We conclude that rituximab can be safely given to people with MMN but in this pilot study we were unable to reduce the amount of IVIg required, at least in the regimen used.     

CADASIL: underdiagnosed in psychiatric patients?

OBJECTIVE: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is exclusively related to symptoms of the central nervous system. Retrospectively in up to 15% the initial presentation is psychiatric disturbances. In these cases the diagnosis often is delayed or missed. METHOD: Two cases of CADASIL diagnosed in a psychiatric hospital are presented. RESULTS: Both patients were admitted to the gerontopsychiatric department (one because of a suicidal attempt and a depressive episode, the other because of cognitive decline and progressive personal neglect). Brain magnetic resonance imaging (MRI) showed severe leukoencephalopathy in the absence of cardiovascular risk factors. In both cases, diagnosis of CADASIL was made by the identification of specific granular osmiophilic material in skin biopsies. CONCLUSION: Brain MRI should be performed in all cases of late onset of severe psychiatric symptoms. CADASIL should be considered as a possible differential diagnosis whenever a marked leukoencephalopathy is detectable. Diagnosis can be verified by taking a skin biopsy or by specific genetic testing.     

Do A‐waves help predict intravenous immunoglobulin response in multifocal motor neuropathy without block?

Introduction: Are there electrophysiological findings that predict response to intravenous immunoglobulin (IVIg) in patients with lower motor neuron (LMN) syndromes without multifocal conduction block (MCB)? Methods: We enrolled 9 patients with LMN syndromes without MCB to receive 18 weeks of IVIg therapy. Response was measured at weeks 2 and 18 using the Appel Amyotrophic Lateral Sclerosis (AALS) score (includes grip and pincer strength measures), ALS Functional Rating Scale (ALSFRS), and electrophysiological measures, including motor unit estimates (MUNEs). Results: No change occurred in AALS or ALSFRS scores posttreatment. Grip/pincer strength increased in 7 patients (P = 0.028) after initial treatment (responders); 2 showed no improvement (non‐responders). No electrophysiological measure changed after treatment in either group but MUNEs trended higher (P = 0.055). “Abnormal A‐waves” (complex, repetitive biphasic, or present in multiple nerves) occurred in pretreatment studies more often in responders (P = 0.028).Discussion:“Abnormal A‐waves” may signal IVIg‐responsive LMN syndromes even if conduction block is absent. Muscle Nerve, 2011     

Are symptoms of peripheral neuropathy more prevalent in patients with Gaucher disease?

BACKGROUND: A previous epidemiological survey from an American referral clinic noted a high incidence of neurological symptoms among patients with type I (non-neuronopathic) Gaucher disease all of whom were treated with specific enzyme replacement. OBJECTIVES: The current study replicates the above in a larger cohort of Ashkenazi Jewish patients with at least one N370S mutation which has been assumed to be protective of neurological involvement. About half the patients had mild disease and were untreated. Methods - Self-reporting questionnaires were sent to patients and their significant others as socio-economically matched controls. RESULTS: There was no significant difference between groups in incidence of concomitant diseases and medications, except patients who reported a significantly higher incidence of vitamin B(12) deficiency and gammopathies. Patients reported significantly higher incidence of virtually all symptoms and signs of peripheral neuropathy and a significantly higher number of symptoms than controls (mean 4.4 vs 2.4). CONCLUSIONS: The conclusion of this study, as of the seminal study, is that the high incidence of neurological complaints in patients with the non-neuronopathic form of Gaucher disease should be viewed in the context of concomitant illnesses, specifically, vitamin B(12) deficiency and gammopathies, regardless of the need for enzyme replacement therapy.     

Hashimoto encephalopathy - is it underdiagnosed in pediatric patients?

Hashimoto encephalopathy (HE) is associated with Hashimoto thyroiditis. Clinically it presents with variable symptoms like seizures, neuropsychiatric changes or focal neurological deficits. Autoimmune phenomena are hypothesized for the pathogenesis. HE has mainly been described in the adult population. We present two 14-year-old patients who presented with recurrent seizures and mental decline. SPECT and PET scans showed distinctly pathological changes. Both patients were diagnosed with HE and improved dramatically on steroids. We feel that HE is a rare but important differential diagnosis of encephalopathy also in the pediatric population. As this disease responds well to steroids, we recommend to obtain basic thyroid function tests as well as thyroid antibodies in all cases of unexplained encephalopathy or unexplained status epilepticus.     

The motor tinel sign: a useful sign in entrapment neuropathy?

The motor Tinel sign (MTS) refers to electromyographic activity, sometimes associated with a visible muscle jerk, evoked by percussion or manipulation of a peripheral nerve. The MTS is found in entrapment neuropathies (such as carpal tunnel syndrome or entrapment of the ulnar nerve at the elbow and peroneal nerve at the fibular head) but occasionally also in normal subjects. The MTS may be useful in evaluating patients with entrapment neuropathy, but it does not always indicate nerve dysfunction.     

Are the EEG microstates correlated with motor and non-motor parameters in patients with Parkinson's disease?

ObjectivesThis study compared electroencephalography microstates (EEG-MS) of patients with Parkinson's disease (PD) to healthy controls and correlated EEG-MS with motor and non-motor aspects of PD.MethodsThis cross-sectional exploratory study was conducted with patients with PD (n = 10) and healthy controls (n = 10) matched by sex and age. We recorded EEG-MS using 32 channels during eyes‐closed and eyes‐open conditions and analyzed the four classic EEG-MS maps (A, B, C, D). Clinical information (e.g., disease duration, medications, levodopa equivalent daily dose), motor (Movement Disorder Society - Unified Parkinson Disease Rating Scale II and III, Timed Up and Go simple and dual-task, and Mini-Balance Evaluation Systems Test) and non-motor aspects (Mini-Mental State Exam [MMSE], verbal fluency, Hospital Anxiety and Depression Scale, and Parkinson's Disease Questionnaire-39 [PDQ-39]) were assessed in the PD group. Mann-Whitney U test was used to compare groups, and Spearman's correlation coefficient to analyze the correlations between coverage of EEG-MS and clinical aspects of PD.ResultsThe PD group showed a shorter duration of EEG-MS C in the eyes-closed condition than the control group. We observed correlations (rho = 0.64 to 0.82) between EEG-MS B, C, and D and non-motor aspects of PD (MMSE, verbal fluency, PDQ-39, and levodopa equivalent daily dose).ConclusionAlterations in EEG-MS and correlations between topographies and cognitive aspects, quality of life, and medication dose indicate that EEG could be used as a PD biomarker. Future studies should investigate these associations using a longitudinal design.     

Are people with dental fear under-represented in oral epidemiological surveys?

Background  

Dental phobia is associated with poorer dental attendance so epidemiological surveys requiring participants to undertake a dental examination may result in an under-representation of participants with high dental fear.     

Sporadic ataxias in Japan – a population-based epidemiological study

Sporadic spinocerebellar ataxias (SCAs) comprise heterogeneous diseases with poorly understood epidemiologies and etiologies. A population-based epidemiological analysis of sporadic ataxias in the Japanese population was described. The prevalence rate of SCAs in the Japanese population is estimated to be 18.5/100,000. Sporadic SCAs account for 67.2% of total SCAs including hereditary SCAs, with olivopontocerebellar atrophy (OPCA) being the most common form sporadic ataxia (64.7%). The natural history analysis conducted on the basis of International Cooperative Ataxia Rating Scale (ICARS) showed that only 33% of patients with OPCA were able to walk at least with one stick 4–5 years after the onset of OPCA, which is much less than that of patients with cortical cerebellar atrophy (CCA). Similarly, 43% of patients with OPCA were able to stand alone 4–5 years after the onset, while 76% of patients with CCA were able to stand alone at the same disease duration. A population–based epidemiological analysis should provide essential information on the natural history of SCAs. *Shoji Tsuji, Osamu Onodera, Ichiro Kanazawa, Hidehiro Mizusawa, Takamichi Hattori, Gen Sobue, Mitsunori Yamada, Yoshiyuki Kuroiwa, Akira Kakizuka, Atsushi Takeda, Kazuko Hasegawa, Tatsuhiko Yuasa, Takemasa Kanda, Kunihiro Yoshida, Teruhiko Kachi, Takashi Nakajima, Mitsuhiro Osame, Sadako Kuno, Kenji Nakajima, Hideshi Kawakami, Yoshitaka Nagai, and Masatoyo Nishizawa.     

Which motor nerve conduction study is best in ulnar neuropathy at the elbow?

There is debate regarding how best to utilize ulnar motor nerve conduction velocity (MNCV) to identify ulnar neuropathy at the elbow (UNE). We used receiver operator characteristic (ROC) curves to compare absolute across-elbow MNCV with MNCV difference between elbow and forearm segments (VDIF) when recording from abductor digiti minimi (ADM) and first dorsal interosseous (FDI) muscles. Also, we determined how their utility was impacted by low amplitudes of compound muscle action potentials (CMAPs). We studied 85 subjects with UNE and 77 subjects with carpal tunnel syndrome but without clinical evidence of UNE. The UNE group was divided into three subgroups based on CMAP amplitude. At 95% specificity, MNCV sensitivities were 80% at ADM and 77% at FDI, and VDIF sensitivities were 51% at ADM and 38% at FDI. The ROC curves showed MNCV to be superior to VDIF across all amplitude subgroups; however, confidence intervals overlapped when amplitude was high.     

Acute motor axonal neuropathy in association with Sjögren syndrome

Sjögren syndrome (SS) has been known to manifest with neurological complications, most frequently of the peripheral nervous system, and often in advance of xerostomia and xerophthalmia. There has been one case report of a patient with SS presenting with acute motor neuropathy similar to Guillain–Barré syndrome (GBS). We report the case of a patient who developed rapidly fulminant acute motor axonal neuropathy (AMAN) with positive anti‐GM1 antibody at high titers in association with serological and pathological evidence of SS without xerostomia or xerophthalmia. Muscle Nerve 42: 828–832, 2010     

Are responsibility beliefs inflated in non-checking OCD patients?

Cognitive models of obsessive-compulsive disorder [e.g., Salkovskis, P. M. (1999). Understanding and treating obsessive-compulsive disorder. Behaviour Research and Therapy, 37(Suppl. 1), S29-S52] propose a key role for inflated responsibility for harm. Studies evaluating such beliefs typically use heterogeneous samples including several OCD subtypes. A recent investigation by Foa et al. [Foa, E. B., Sacks, M. B., Tolin, D. F., Prezworski, A., & Amir, N. (2002). Inflated perception of responsibility for harm in OCD patients with and without checking compulsions: a replication and extension. Journal of Anxiety Disorders, 16(4), 443-453] found responsibility to be elevated in OC checkers, but not in non-checking OCD patients, relative to non-anxious controls. In that study, the responsibility measure included checking scenarios, thus leaving the possibility that these findings may have been due to criterion contamination. The present study investigated responsibility beliefs in OC checkers (n=39) and non-checkers (n=20), anxious controls (n=22), and non-clinical controls (n=69), using measures of responsibility which do not have item overlap with OCD symptoms. Results indicated that both OC groups showed greater responsibility beliefs relative to anxious and non-anxious controls. OC checkers endorsed greater responsibility appraisals than anxious and non-clinical control groups. In contrast, non-checking OCs reported greater responsibility appraisals than non-clinical controls, but did not differ from anxious controls and OC checkers. Results are discussed in the context of the cognitive model of OCD.     

Chronic inflammatory demyelinating polyneuropathy or hereditary motor and sensory neuropathy?

The pathological changes generally considered to distinguish chronic inflammatory demyelinating polyneuropathy (CIDP) from hereditary motor and sensory neuropathy (HMSN) are: mononuclear cell infiltrates, prominent endoneurial oedema, and marked fascicle-to-fascicle variability. We evaluated the diagnostic significance of these pathological features which are suggestive of CIDP. Nerve biopsies from 42 dominant HMSN type I cases with a normal disease course were investigated for the occurrence of inflammatory features. A small cluster of mononuclear cells was found in 12% of the cases and marked endoneurial oedema in 21%. Variability in pathology between the fascicles was not observed. The histogram configuration yielded additional information for differential diagnosis. Subsequently, we reviewed the clinical, electrophysiological and morphological features of 18 sporadic cases of chronic progressive demyelinating motor and sensory neuropathy with mainly classic onion bulbs in their nerve biopsies and a disease onset in the first decade. In all these patients DNA investigation for the 17p11.2 duplication was performed. According to the results of the DNA investigation, autosomal dominant HMSN type Ia was diagnosed in eight patients, although in six slight CIDP-positive features were present. A diagnosis was definite or most probable CIDP in eight patients. In two patients no definite diagnosis could be made. Testing for the presence of the 17p11.2 duplication is, therefore, helpful in distinguishing between CIDP and HMSN type I. The diagnosis of CIDP requires careful evaluation of the clinical, electrophysiological and morphological data to avoid false-positive diagnoses of inflammatory disorders.