Optic, trigeminal, and facial neuropathy related to anti-neurofascin 155 antibody.

OBJECTIVE: To characterize the frequency and patterns of optic, trigeminal, and facial nerve involvement by neuroimaging and electrophysiology in IgG4 anti-neurofascin 155 antibody-positive (NF155+ ) chronic inflammatory demyelinating polyneuropathy (CIDP). METHODS: Thirteen IgG4 NF155+ CIDP patients with mean onset age of 34 years (11 men) were subjected to neurological examination, blink reflex, and visual-evoked potential (VEP) testing, and axial and/or coronal T2-weighted head magnetic resonance imaging (MRI). RESULTS: Among 13 patients, facial sensory impairment, facial weakness, and apparent visual impairment were observed in three (23.1%), two (15.4%), and two (15.4%) patients, respectively. All 12 patients tested had blink reflex abnormalities: absent and/or delayed R1 in 11 (91.7%), and absent and/or delayed R2 in 10 (83.3%). R1 latencies had strong positive correlations with serum anti-NF155 antibody levels (r = 0.9, P ≤ 0.0001 on both sides) and distal and F wave latencies of the median and ulnar nerves. Absent and/or prolonged VEPs were observed in 10/13 (76.9%) patients and 17/26 (65.4%) eyes. On MRI, hypertrophy, and high signal intensity of trigeminal nerves were detected in 9/13 (69.2%) and 10/13 (76.9%) patients, respectively, whereas optic nerves were normal in all patients. The intra-orbital trigeminal nerve width on coronal sections showed a significant positive correlation with disease duration. INTERPRETATION: Subclinical demyelination frequently occurs in the optic, trigeminal, and facial nerves in IgG4 NF155+ CIDP, suggesting that both central and peripheral myelin structures of the cranial nerves are involved in this condition, whereas nerve hypertrophy only develops in myelinated peripheral nerve fibers.

A case of overlapping adult-onset linear scleroderma and Parry-Romberg syndrome presenting with widespread ipsilateral neurogenic involvement.

Linear scleroderma is a variant of localized scleroderma. We report a 43-year-old woman who had developed left arm weakness and linear scleroderma on her back during pregnancy at 25 years of age, followed by left hemifacial atrophy and left leg weakness. She had multiple linear scleroderma lesions on her trunk and left limbs, left eyelid ptosis, impairment of vertical movement and abduction of the left eye, left hemifacial atrophy, and weakness and atrophy of the sternocleidomastoid, trapezius, and proximal limb muscles on the left side. On serology, antibodies to U1-ribonucleoprotein and Jo-1 were positive; anti-scleroderma-70 antibody was negative. Skin biopsy demonstrated increased hypertrophic collagen fibers without inflammatory infiltrates. Needle electromyography of left limb muscles revealed mild neurogenic patterns; left quadriceps muscle biopsy showed chronic neurogenic changes. Brain magnetic resonance imaging revealed mild left hemispheric atrophy. This is a rare case of linear scleroderma and Parry-Romberg syndrome presenting with widespread ipsilateral neurogenic manifestations.

Neuromagnetic correlates of hemispheric specialization for face and word recognition.

The adult human brain appears to have specialized and independent neural systems for the visual processing of faces and words: greater selectivity for faces in the right hemisphere (RH) while greater selectivity for words in the left hemisphere (LH). Nevertheless, the nature of functional differences between the hemispheres is still largely unknown. To elucidate the hemispheric specialization for face and word recognition, event-related magnetic fields (ERFs) were recorded in young adults while they passively viewed faces and words presented either in the right visual field or in the left visual field. If the neural correlates of face recognition and word recognition reflect the same lateralization profile, then the lateralization of the magnetic source of the M170 component should follow a similar profile, with a greater M170 response for faces in the RH and a greater M170 response for words in the LH. We observed the expected finding of a larger M170 in the LH for words. Unexpectedly, a larger M170 response in the RH for faces was not found. Thus, the hemispheric organization of face recognition is different from that of word recognition in terms of specificity.

Decreased stimulus-driven connectivity of the primary visual cortex during visual motion stimulation in amnestic mild cognitive impairment: An fMRI study.

Motion perceptual deficits are common in Alzheimer's disease (AD). Although the posterior parietal cortex is thought to play a critical role in these deficits, it is currently unclear whether the primary visual cortex (V1) contributes to these deficits in AD. To elucidate this issue, we investigated the net activity or connectivity within V1 in 17 amnestic mild cognitive impairment (aMCI) patients, 17 AD patients and 17 normal controls (NC) using functional magnetic resonance imaging (fMRI). fMRI was recorded under two conditions: visual motion stimulation and resting-state. The net activity or connectivity within V1 extracted by independent component analysis (ICA) was significantly increased during visual motion stimuli compared with that of the resting-state condition in NC, but not in aMCI or AD patients. These findings suggest the alteration of the net activity or connectivity within V1, which may contribute to the previously reported motion perceptual deficits in aMCI and AD. Therefore, the decreased net V1 activity measured as the strength of the ICA component may provide a new disease biomarker for early detection of AD.

[A case of possible elderly onset rheumatoid meningitis without arthritis].

A 93-year-old man was admitted to our hospital with disturbance of consciousness. Brain magnetic resonance imaging (MRI) showed hyperintensity of the subarachnoid space in the left frontal and parietal lobes on diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR). Gadolinium-enhancement of the pia mater was also observed. We did not perform biopsy because of a high risk of perioperative complication. Although physical examination found no evidence of the rheumatoid arthritis, rheumatoid factors and anti-cyclic citrullinated peptides antibodies were elevated. He was suspected to have rheumatoid meningitis. We treated him with intravenous methylprednisolone (0.5 g/day) for 3 days. Rheumatoid meningitis often shows hyperintensity of the subarachnoid space on the DWI and FLAIR, and steroid therapy is effective.

Mutations in MME cause an autosomal-recessive Charcot-Marie-Tooth disease type 2.

OBJECTIVE: The objective of this study was to identify new causes of Charcot-Marie-Tooth (CMT) disease in patients with autosomal-recessive (AR) CMT. METHODS: To efficiently identify novel causative genes for AR-CMT, we analyzed 303 unrelated Japanese patients with CMT using whole-exome sequencing and extracted recessive variants/genes shared among multiple patients. We performed mutation screening of the newly identified membrane metalloendopeptidase (MME) gene in 354 additional patients with CMT. We clinically, genetically, pathologically, and radiologically examined 10 patients with the MME mutation. RESULTS: We identified recessive mutations in MME in 10 patients. The MME gene encodes neprilysin (NEP), which is well known to be one of the most prominent beta-amyloid (Aß)-degrading enzymes. All patients had a similar phenotype consistent with late-onset axonal neuropathy. They showed muscle weakness, atrophy, and sensory disturbance in the lower extremities. All the MME mutations could be loss-of-function mutations, and we confirmed a lack/decrease of NEP protein expression in a peripheral nerve. No patients showed symptoms of dementia, and 1 patient showed no excess Aß in Pittsburgh compound-B positron emission tomography imaging. INTERPRETATION: Our results indicate that loss-of-function MME mutations are the most frequent cause of adult-onset AR-CMT2 in Japan, and we propose that this new disease should be termed AR-CMT2T. A loss-of-function MME mutation did not cause early-onset Alzheimer's disease. Identifying the MME mutation responsible for AR-CMT could improve the rate of molecular diagnosis and the understanding of the molecular mechanisms of CMT.

Analysis of cerebral lobar microbleeds and a decreased cerebral blood flow in a memory clinic setting.

OBJECTIVE: Cerebral microbleeds (MBs) have been previously associated with cognitive dysfunction, including Alzheimer's disease. In the present study, we aimed to clarify the relationship between cerebral lobar MBs and the regional cerebral blood flow (CBF). METHODS: We investigated the data obtained from 122 patients in our memory clinic who were examined by both MRI and (99m)Tc-ethyl cysteinate dimer (ECD)-single photon emission computed tomography (SPECT). Patient brain scans were superimposed and brain regions containing both decreased CBF and MBs were visually identified. For each patient eight brain regions were evaluated, comprising the right and left frontal, temporal, parietal, and occipital lobes. RESULTS: Cerebral MBs were detected in 36 of the 122 (29.5%) patients. Of these 36 patients, 23 had detectable lobar MBs, which were primarily distributed in the occipital lobe in 19 of the 46 (41.3%) regions with lobar MBs. The frequency of MBs accompanied by a decreased CBF in the parietal and occipital lobes was significantly higher than that observed in the frontal lobe (73.3% vs. 27.3%, p<0.05, and 73.7% vs. 27.3%, p<0.05, respectively). Additionally, a decreased CBF was observed significantly more frequently in the brain regions with 5 or more MBs compared to the regions with one microbleed (83.3 vs. 25.0%, p<0.0005). Among the 17 patients with observable MBs accompanied by a decreased CBF, none were initially diagnosed with either subjective complaints or mild cognitive impairment. CONCLUSION: We determined that the cerebral lobar MBs located in the parietal and occipital lobes, and the lobar regions with a large number of MBs, were significantly more likely to be accompanied by a decreased CBF.

[Electrophysiological diagnosis of multiple sclerosis].

Evoked potentials (EPs) in a daily practice consist of somatosensory evoked potentials (SEP), visual evoked potentials (VEP), auditory brainstem response (ABR) and motor evoked potentials (MEP). EPs can confirm the presence of lesions in patients with suspected involvement, and document the presence of clinically unsuspected lesions in multiple sclerosis (MS) patients. MEP has the highest sensitivity while VEP is the second sensitive. Furthermore, we are able to obtain an increase in sensitivity by using multimodality evoked potentials (MuEP). By doing so, there is a significant correlation between EP abnormalities and Expanded Disability Status Scale. Thus, EPs are useful for the diagnosis or evaluation of MS and predicting neurological disabilities.

Evaluation of polyglutamine repeats in autosomal dominant Parkinson's disease.

We evaluated the contributions of various polyglutamine (polyQ) disease genes to Parkinson's disease (PD). We compared the distributions of polyQ repeat lengths in 8 common genes (ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, TBP, ATN1, and HTT) in 299 unrelated patients with autosomal dominant PD (ADPD) and 329 normal controls. We also analyzed the possibility of genetic interactions between ATXN1 and ATXN2, ATXN2 and ATXN3, and ATXN2 and CACNA1A. Intermediate-length polyQ expansions (>24 Qs) of ATXN2 were found in 7 ADPD patients and no controls (7/299 = 2.34% and 0/329 = 0%, respectively; p = 0.0053 < 0.05/8 after Bonferroni correction). These patients showed typical L-DOPA-responsive PD phenotypes. Conversely, no significant differences in polyQ repeat lengths were found between the ADPD patients and the controls for the other 7 genes. Our results may support the hypothesis that ATXN2 polyQ expansion is a specific predisposing factor for multiple neurodegenerative diseases.

[A case of acute autonomic, sensory and motor neuropathy with swelling and gadolinium enhancement of bilateral trigeminal nerve on MRI and dissociation between superficial and deep sensation disturbance].

We report a case of a 46-year old man with acute autonomic, sensory and motor neuropathy (AASMN). He developed severe orthostatic hypotension, anuria,anhydrosis, tonic pupil with dysarthria, dysphagia, jaw claudication, and dysesthesia and sharp pain several days after symptom of upper respiratory infection. Neurological examination revealed severely decreased superficial sensation with normal deep sensation. Brain MRI findings showed bilateral trigeminal nerve swelling with gadolinium (Gd) enhancement. His motor and sensory symptoms and MRI abnormality were improved after the administration of intravenous immunoglobulin and intravenous methylprednisolone therapy; however his autonomic symptoms scarcely reacted to these immunotherapies. As long as we investigated in AASMN cases, bilateral trigeminal nerve swelling with Gd enhancement and dissociation between superficial and deep sensation disturbance have not reported, suggesting that the present case mainly disrupted C nerve fibers distributing postganglionic autonomic and temperature-pain sensory nerves.