Peripheral neuropathy in a case with CADASIL: a case report.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized clinically by central nervous system dysfunctions. It is unclear whether CADASIL is involved in peripheral neuropathy. CASE PRESENTATION: A 67-year-old Japanese man with stepwise progression of sensory and motor neuropathy was admitted to our hospital. Peripheral neuropathy of the extremities was detected through electrophysiological and pathological studies, and brain magnetic resonance imaging revealed bilateral periventricular ischemic and thalamic hemorrhagic lesions. We diagnosed CADASIL after detecting granular osmiophilic material in the walls of the endoneurial vessels morphologically and identifying a heterozygous NOTCH3 mutation p.Arg75Pro. CONCLUSIONS: CADASIL is to be included in the work-up of not classified peripheral neuropathies.

Neurofilament light mutation causes hereditary motor and sensory neuropathy with pyramidal signs.

To identify novel mutations causing hereditary motor and sensory neuropathy (HMSN) with pyramidal signs, a variant of Charcot-Marie-Tooth disease (CMT), we screened 28 CMT and related genes in four members of an affected Japanese family. Clinical features included weakness of distal lower limb muscles, foot deformity, and mild sensory loss, then late onset of progressive spasticity. Electrophysiological studies revealed widespread neuropathy. Electron microscopic analysis showed abnormal mitochondria and mitochondrial accumulation in the neurons and Schwann cells. Brain magnetic resonance imaging (MRI) revealed an abnormally thin corpus callosum. In all four, microarrays detected a novel heterozygous missense mutation c.1166A>G (p.Y389C) in the gene encoding the light-chain neurofilament protein (NEFL), indicating that NEFL mutations can result in a HMSN with pyramidal signs phenotype.

Neuromyelitis optica spectrum disorder safely and successfully treated with satralizumab during pregnancy and breastfeeding: a case report.

Background: Satralizumab, a monoclonal antibody that recognizes interleukin-6 receptors, is known to reduce the relapse rate in neuromyelitis optica spectrum disorder (NMOSD), but its safety during pregnancy has not been established. We present the case of an NMOSD patient who safely completed pregnancy, parturition, and breastfeeding under satralizumab treatment. Importantly, satralizumab transfer to umbilical cord blood, infant serum, or breast milk was not observed. Case presentation: A 37-year-old Japanese female developed anti-aquaporin 4 antibody-positive NMOSD with left optic neuritis. Despite responding to steroid and azathioprine therapy, she experienced moon face and weight gain and desired the prompt reduction of the steroid dosage. She also wanted to conceive a child with a safe and preferably early pregnancy and parturition. Because pregnancy and parturition after the onset of NMOSD elevate the risk of relapse and miscarriage, treatment with satralizumab was initiated with the patient's consent. She experienced normal parturition and continued with satralizumab, steroid, and azathioprine treatments while breastfeeding without experiencing any relapses. Concentrations of satralizumab in the umbilical cord blood, infant serum, and breast milk were below the detection sensitivity. Conclusion: These findings suggest that satralizumab may be safe and effective for the perinatal management of NMOSD, especially when there are concerns about continuing pregnancy and the risk of relapse after parturition.

Role of ubiquitin-proteasome proteolysis in muscle fiber destruction in experimental chloroquine-induced myopathy.

Previous studies have documented the presence of rimmed vacuoles, atrophic fibers, and increased lysosomal cathepsin activity in skeletal muscle from animal models of chloroquine-induced myopathy, suggesting that muscle fibers in this type of myopathy may be degraded via the lysosomal-proteolysis pathway. Given recent evidence of abnormal ubiquitin accumulation in rimmed vacuoles, in this study we chose to examine the significance of the ubiquitin-proteasome proteolytic system in the process of muscle fiber destruction in experimental chloroquine myopathy. Expression of ubiquitin, 26S proteasome proteins, and ubiquitin ligases, such as muscle-specific RING finger-1 (MuRF-1) and atrogin-1/muscle atrophy F-box protein (MAFbx), was analyzed in innervated and denervated rat soleus muscles after treatment with either saline or chloroquine. Abnormal accumulation of rimmed vacuoles was observed only in chloroquine-treated denervated muscles. Ubiquitin and proteasome immunostaining, and ubiquitin, MuRF-1, and atrogin-1/MAFbx mRNAs were significantly increased in denervated soleus muscles from saline- and chloroquine-treated rats when compared with contralateral innervated muscles. Further, ubiquitin and ubiquitin ligase mRNA levels were higher in denervated muscles from chloroquine-treated rats when compared with saline-treated rats. These data demonstrate increased proteasomes and ubiquitin in denervated muscles from chloroquine-treated rats and suggest that the ubiquitin-proteasome proteolysis pathway as well as the lysosomal-proteolysis pathway mediate muscle fiber destruction in experimental chloroquine myopathy.