A case of cystinuria presenting with cerebellar ataxia and dementia.

Cystinuria normally manifests as recurrent urinary stones and renal dysfunction, but can present to neurologists with ataxia, posterior column impairment, intellectual deficiency and pyramidal and extrapyramidal signs; the neuroradiological features include cerebellar, brainstem and cerebral atrophy. It is an autosomal recessive disease caused by a transport disorder of cystine and dibasic amino acids in renal proximal tubules. Most cases have an SLC3A1 and/or SLC7A9 gene mutation but some recent Japanese patients have had distinct heterozygous gene mutations. We report a patient with cystinuria with a heterozygous P482L mutation in the SLC7A9 gene, presenting with atrophy in the cerebellum, brainstem and cerebrum and with no urinary stones. Cystine, an amino acid comprising two cysteine molecules, is transported into cells via a cystine transporter. It is essential for producing hydrogen sulfate and the cellular antioxidant glutathione: these exert neuroprotection in astrocytes and cerebellar Purkinje cells. Although cystinuria is a metabolic disorder associated with renal dysfunction, we suspect that a trafficking defect of transporter rBAT-BAT1 in brain might cause neuronal degeneration, leading to cerebellar and cerebral atrophy.

[Primary central nervous system lymphoma presenting as a unilateral internal auditory canal lesion: a case report].

A 61-year-old man with right hearing loss and staggering for seven months was diagnosed with sudden deafness although previous evaluation with MRI indicated minor abnormal findings. During follow-up, he developed hypogeusia, right facial nerve palsy, pain in right mandible, right-sided temporal pain, and cerebellar ataxia. Cerebrospinal fluid examination at admission revealed reduced glucose concentration and elevated soluble interleukin-2 receptor (sIL-2R) level, whereas serum sIL-2R level was within the normal range. Brain MRI showed a swollen contrast-enhanced lesion extending from the right internal auditory canal to the middle cerebellar peduncle. Gallium-67 (67Ga) single-photon emission-computed tomography-computed tomography (SPECT-CT) revealed abnormal accumulation at the lesion site. Pathologic analysis of the tumor after resection led to the diagnosis of primary central nervous system lymphoma. In the present case, the MRI and 67Ga SPECT-CT characteristics were distinct from those of vestibular schwannoma. In addition, elevation of sIL-2R in the cerebrospinal fluid but not in serum was useful for differential diagnosis.

Subthalamic nucleus deep brain stimulation restores normal rapid eye movement sleep in Parkinson's disease.

BACKGROUND: In Parkinson's disease, sleep disturbance is a common occurrence. METHODS: We evaluated sleep in 10 patients with Parkinson's disease (age, 57.5 ± 9.8 years; disease duration, 12.3 ± 2.7 years) before and after subthalamic nucleus deep brain stimulation using the Parkinson's disease sleep scale and polysomnography. RESULTS: Their total sleep scale scores and daytime sleepiness subscale scores significantly improved after subthalamic nucleus-deep brain stimulation. The novel findings from this study significantly increased normal rapid eye movement sleep, and decreased abnormal rapid eye movement sleep without atonia after deep brain stimulation in patients with Parkinson's disease. The improved total sleep scale score correlated with decreased wakefulness after sleep onset. Moreover, improved daytime sleepiness correlated with increased normal rapid eye movement sleep time. Sleep improvement did not significantly correlate with resolution of motor complication or reduced dopaminergic dosages. CONCLUSIONS: Subthalamic nucleus-deep brain stimulation may have beneficial effects on sleep disturbance in advanced Parkinson's disease by restoring sleep architecture and normal rapid eye movement sleep.

Novel pathogenic mutations and copy number variations in the VPS13A gene in patients with chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a rare autosomal recessive neurodegenerative disorder caused by loss of function mutations in the vacuolar protein sorting 13 homolog A (VPS13A) gene that encodes chorein. It is characterized by adult-onset chorea, peripheral acanthocytes, and neuropsychiatric symptoms. In the present study, we performed a comprehensive mutation screen, including sequencing and copy number variation (CNV) analysis, of the VPS13A gene in ChAc patients. All 73 exons and flanking regions of VPS13A were sequenced in 35 patients diagnosed with ChAc. To detect CNVs, we also performed real-time quantitative PCR and long-range PCR analyses for the VPS13A gene on patients in whom only a single heterozygous mutation was detected. We identified 36 pathogenic mutations, 20 of which were previously unreported, including two novel CNVs. In addition, we investigated the expression of chorein in 16 patients by Western blotting of erythrocyte ghosts. This demonstrated the complete absence of chorein in patients with pathogenic mutations. This comprehensive screen provides an accurate and useful method for the molecular diagnosis of ChAc.

[Cerebral amyloid angiopathy-related transient focal neurological episodes with diffusion-weighted imaging hyperintense lesions in subcortical white matter and cortical superficial siderosis].

A 72-year-old man presented with two episodes of migratory left-sided paresthesia lasting 10 min. At the first episode, diffusion-weighted imaging hyperintense lesions (DWIHLs) were seen in the right parietal lobe, suggesting an initial diagnosis of acute ischemic stroke, for which we administered antiplatelet therapy for secondary prevention. Four months later, he again developed transient migratory left-sided paresthesia. Gradient-echo T2*-weighted imaging at this time showed disseminated cortical superficial siderosis (cSS) and strictly cerebral microbleeds around the DWIHLs in the right parietal lobe. These findings led to a diagnosis of cerebral amyloid angiopathy and its related findings, including transient focal neurological episodes (TFNE) and DWIHLs, and antiplatelet medication was stopped. In clinical settings, although it is challenging to distinguish TFNE of hemorrhagic origin from cerebral ischemic symptoms, including transient ischemic attacks, this case suggests that even when elderly patients with transient neurological symptoms present with cortical DWIHLs, paramagnetic-sensitive MRI should be performed to check for cSS around the DWIHLs.

Zonisamide attenuates the severity of levodopa-induced dyskinesia via modulation of the striatal serotonergic system in a rat model of Parkinson's disease.

Glutamate, GABA, acetylcholine, dopamine, and serotonin interact with each other to regulate the flow of neural information in the striatum. Serotonin type 1A receptor (5HT1A) is primarily expressed on glutamatergic nerve terminals, and 5HT1B is expressed on GABAergic medium spiny neurons (MSNs). Zonisamide (ZNS) reportedly improves the off period without worsening levodopa-induced dyskinesia (LID) in patients with advanced Parkinson's disease. In this study, LID model rats were prepared by administrating levodopa to unilaterally 6-OHDA-lesioned rats. We analyzed changes in serotonergic neurotransmission of LID model rats to elucidate the relationship between LID and the serotonergic system and pathomechanism of the anti-dyskinetic effects of ZNS. Abnormal involuntary movements (AIMs) were most severe in intermittently levodopa-treated rats but milder in rats intermittently medicated with levodopa and ZNS. Continuously levodopa-infused rats or intermittently ZNS-injected rats did not develop AIMs, and no differences in the expression of brain-derived neurotrophic factor, 5-HT transporter, 5HT1A, and 5HT1B mRNA between the lesioned striatum and normal side were observed. Expression of 5HT1B mRNA was elevated in the lesioned striatum of intermittently levodopa-treated rats, but this elevation was normalized by concomitant use of ZNS. The severity of AIMs was correlated with the ratio of 5HT1B to 5HT1A mRNA expression in the lesioned striatum, indicating that the anti-LID effect of ZNS is based on inhibition via 5HT1B receptors to direct pathway MSNs sensitized by intermittent levodopa treatment. Selectively acting serotonergic drugs, especially those that lower the 5HT1B to 5HT1A ratio, are promising new therapeutic agents to attenuate LID development.

Cerebrospinal Fluid Rhinorrhea and Subsequent Bacterial Meningitis due to an Atypical Clival Fracture.

Cases of cerebrospinal fluid (CSF) rhinorrhea due to clival fracture are rare. We present a case of bacterial meningitis with CSF rhinorrhea after a clival fracture. Heavily T2-weighted images showed a bone flap in the thinned clivus and fluid collection in the sphenoid sinus. CSF rhinorrhea developed at 1 month after mild trauma. The fracture may have been caused by the trauma and/or by the pressure gradient between the intracranial CSF space and the sphenoid sinus. A detailed history to identify trauma and an examination to detect bone defects in the skull base are necessary when patients present with bacterial meningitis and persistent rhinorrhea.

Longitudinally Extensive Transverse Myelitis and Optic Neuropathy Associated with Syphilitic Meningomyelitis and Human Immunodeficiency Virus Infection: A Case Report and Review of the Literature.

The incidence of co-infection with Treponema pallidum and human immunodeficiency virus (HIV) is increasing in developing and developed countries. The neurological complications of both infections occasionally occur simultaneously during a clinical course. We herein report the case of an HIV carrier with syphilitic meningomyelitis and subclinical optic neuropathy. The patient presumably had latent syphilis and slowly developed longitudinally extensive transverse myelitis (LETM). A cerebrospinal fluid examination confirmed the diagnosis of active neurosyphilis based on an elevated T. pallidum hemagglutination assay index. A change in the patient's immune status, possibly due to HIV, might have converted the syphilis from latent to active, leading to LETM of the spinal cord.

Two cases of acute myelitis with idiopathic hypereosinophilic syndrome.

Idiopathic hypereosinophilic syndrome (IHES) is characterised by persistent eosinophilia and organ damage after ruling out other causes. IHES is clinically and pathologically heterogeneous, and several disease mechanisms have been described. Although neurological involvement with IHES is extremely rare, we report the first cases of acute myelitis with IHES, which are confirmed using MRI, fulfil the diagnostic criteria of IHES and pathologically reveal eosinophilic tissue infiltration in the liver and skin. Patient 1 had longitudinally extensive transverse myelitis, which developed in the absence of steroid therapy. Patient 2 developed acute myelitis with two short lesions during a 3 mg/day corticosteroid treatment. Both cases had eosinophilia (>1500/mm(3)) at the onset of myelitis. These findings suggest that earlier treatment and a sufficient dose of corticosteroids may prevent the lesional expansion in acute myelitis. Steroid therapy should be initiated early before organ involvement, because permanent neuronal damage with a larger lesion becomes more critical.

A case of chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) in East Asia.

Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS) syndrome is a clinically and radiologically distinct pontine-predominant perivascular neuroinflammation showing T lymphocyte infiltration. It is assumed to have an autoimmune or other inflammatory mediated pathogenesis. We report the first known case of CLIPPERS in East Asia, characterized by multiple punctate enhancement of the brainstem extending to the bilateral posterior limb of the internal capsule and caudal to the spinal cord conus. The patient had elevated IgE levels and a history of allergies, suggesting that lesions may arise from neuroinflammation in response to T lymphocyte infiltration into perivascular spaces.