ABSTRACT
BACKGROUND: Despite the suggestion that direct compression by granuloma and ischemia resulting from vasculitis can cause nerve fiber damage, the mechanisms underlying sarcoid neuropathy have not yet been fully clarified. METHODS: We examined the clinicopathological features of sarcoid neuropathy by focusing on electrophysiological and histopathological findings of sural nerve biopsy specimens. We included 18 patients with sarcoid neuropathy who had non-caseating epithelioid cell granuloma in their sural nerve biopsy specimens. RESULTS: Although electrophysiological findings suggestive of axonal neuropathy were observed, particularly in the lower limbs, all but three patients showed ≥1 abnormalities in nerve conduction velocity or distal motor latency. Additionally, a conduction block was observed in 11 of the 16 patients for whom waveforms were assessed; five of them fulfilled motor nerve conduction criteria strongly supportive of demyelination as defined in the European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) guideline for chronic inflammatory demyelinating polyneuropathy (CIDP). In most patients, sural nerve biopsy specimens revealed a mild to moderate degree of myelinated fiber loss. Fibrinoid necrosis was observed in one patient, and electron microscopy analysis revealed demyelinated axons close to granulomas in six patients. CONCLUSIONS: Patients with sarcoid neuropathy may meet the EAN/PNS electrophysiological criteria for CIDP due to the frequent presence of conduction blocks. Based on our results, in addition to the ischemic damage resulting from granulomatous inflammation, demyelination may play an important role in the mechanism underlying sarcoid neuropathy.
Subject(s)
Polyradiculoneuropathy, Chronic Inflammatory Demyelinating , Vasculitis , Humans , Peripheral Nerves/pathology , Granuloma/pathology , Neural Conduction/physiology , Vasculitis/pathology , Sural Nerve/pathologyABSTRACT
Autosomal recessive cerebellar ataxias and autosomal recessive hereditary spastic paraplegias are clinically and genetically heterogeneous disorders with diverse neurological and non-neurological features. We herein describe a Japanese patient with a slowly progressive form of ataxia and spastic paraplegia. Using whole exome sequencing, we identified a novel homozygous frameshift mutation in SPG7, encoding paraplegin, in this patient. This is the first report of an SPG7 mutation in the Japanese population. For disorders previously undetected in a particular population, or unrecognized/atypical phenotypes, exome sequencing may facilitate molecular diagnosis.
Subject(s)
Asian People/genetics , Intellectual Disability/genetics , Metalloendopeptidases/genetics , Muscle Spasticity/genetics , Mutation/genetics , Optic Atrophy/genetics , Paraplegia/genetics , Spastic Paraplegia, Hereditary/genetics , Spinocerebellar Ataxias/genetics , ATPases Associated with Diverse Cellular Activities , Exome/genetics , Homozygote , Humans , Intellectual Disability/diagnosis , Male , Middle Aged , Muscle Spasticity/diagnosis , Optic Atrophy/diagnosis , Paraplegia/diagnosis , Pedigree , Sequence Analysis, DNA/methods , Spastic Paraplegia, Hereditary/diagnosis , Spinocerebellar Ataxias/diagnosisABSTRACT
BACKGROUND: Chronic dizziness is frequently reported by patients in the chronic stage after ischemic stroke. The aim of this study was to determine the efficacy of cilostazol versus that of aspirin for the chronic dizziness that follows ischemic stroke. METHODS: We performed a prospective, randomized, open-label, blinded endpoint trial. One hundred six patients who suffered supratentorial ischemic stroke within the previous 1-6 months and subsequently complained of persistent dizziness without other obvious sequelae were enrolled. Patients were randomly given cilostazol (200mg/day) or aspirin (100mg/day) for 6 months. Rates of improvement in the dizziness were then evaluated. Changes in fixation suppression of the vestibulo-ocular reflex (an indicator of cerebral control over the brainstem reflex related to balance), regional cerebral blood flow (CBF) in the cerebrum, cerebellum, and brainstem; and the Zung Self-Rating Depression Scale (SDS) were also evaluated. RESULTS: Dizziness was significantly improved in the cilostazol group versus the aspirin group (P<0.0001) after the 6-month therapy. The capacity for fixation suppression of the vestibulo-ocular reflex was improved (P<0.0001), and regional CBF in the cerebrum (relative to that in the brainstem [P=0.003] and to that in the cerebello-brainstem [P=0.012]) was increased only in the cilostazol group. There was no statistical difference in the change in SDS scores between the two groups. CONCLUSION: Cilostazol improves the chronic dizziness that follows ischemic stroke and increases supratentorial CBF and cerebral function for adaptation of the brainstem reflex related to the sense of balance.
