Favorable Outcome with Intravenous Immunoglobulin Therapy in Late-Onset Anti-mGluR1 Encephalitis: A Case Report and Literature Review.

Anti-metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare autoimmune disorder manifesting with cerebellar syndrome. Patients with mGluR1 encephalitis have been treated with immunomodulatory therapies; however, little is known about the efficacy of this therapy. A 58-year-old Japanese woman presented with dizziness when walking and standing up. Symptoms persisted and the patient gradually deteriorated. The neurological examination revealed a broad-based gait, horizontal and slightly gaze-evoked nystagmus, noticeable head titubation, and truncal ataxia without limb ataxia. Magnetic resonance imaging was normal. The 123I-isopropyl-iodoamphetamine single-photon emission-computed tomography scans showed normal cerebellar perfusion. Based on a positive antibody test for anti-mGluR1, the patient was diagnosed with anti-mGluR1 encephalitis. She was treated with intravenous methylprednisolone and intravenous immunoglobulin (IVIg). Symptoms gradually improved over 1 month and almost disappeared after additional IVIg therapy. Anti-mGluR1 encephalitis is a rare disease, and effective treatment is unclear. In this case, a favorable outcome was obtained with immunomodulatory therapy, even though the neurological disability of the disease course is worse. We emphasize the importance of early diagnosis and therapeutic intervention, suspecting the disease on the basis of its characteristic symptoms.

Somatic instability of CTG repeats in the cerebellum of myotonic dystrophy type 1.

INTRODUCTION: We statistically analyzed somatic instability of the CTG expansion in the central nervous system and visceral organs in 7 patients with myotonic dystrophy type 1 and also report intracerebellar instability in 2 patients. METHODS: CTG repeat expansion was estimated in the samples from autopsied brains and visceral organs by Southern blot analysis. Pathological study was performed. Samples were taken from several sites in the cerebellum to examine intracerebellar instability. RESULTS: The CTG repeat expansion was shortest in the cerebellar cortex among all tissues examined. With regard to the intracerebellar difference, the shortest expansion was seen in the cortices of the hemisphere and vermis, whereas it was moderate in the dentate nucleus and longest in the white matter of the hemisphere and middle cerebellar peduncle. CONCLUSIONS: The shortest expansion might be attributable to packed granule cells in the cerebellar cortex. Further analysis of cell-specific methylation states might elucidate the enigma of somatic instability.

Neuropathology does not Correlate with Regional Differences in the Extent of Expansion of CTG Repeats in the Brain with Myotonic Dystrophy Type 1.

Myotonic dystrophy (DM1) is known to be an adult-onset muscular dystrophy caused by the expansion of CTG repeats within the 3' untranslated region of the dystrophin myotonin protein kinase (DMPK) gene. The clinical features of DM1 include CNS symptoms, such as cognitive impairment and personality changes, the pathogenesis of which remains to be elucidated. We hypothesized that the distribution of neuropathological changes might be correlated with the extent of the length of the CTG repeats in the DMPK genes in DM1 patients. We studied the neuropathological changes in the brains of subjects with DM1 and investigated the extent of somatic instability in terms of CTG repeat expansion in the different brain regions of the same individuals by Southern blot analysis. The neuropathological changes included état criblé in the cerebral deep white matter and neurofibrillary tangles immunoreactive for phosphorylated tau in the hippocampus and entorhinal cortex, both of which were compatible with the subcortical dementia in DM1 patients. However, the length of the CTG repeats did not correlate with the regional differences in the extent of neuropathological changes. Our data suggested that pathomechanisms of dementia in DM1 might be more multifactorial rather than a toxic gain-of-function due to mutant RNA.

[Four siblings with becker muscular dystrophy (BMD) manifesting severe mental retardation].

A 33-year-old man with BMD manifesting severe mental retardation is reported. This patient has mild pseudohypertrophy in his calf muscles and showed an elevation of creatine kinase (CK) level in the serum (2215 IU/L). He was diagnosed as autistic at the age of three. His intellectual level was estimated to be two years old in social intelligence and four months old in speech ability at the age of 33. However his muscle strength remains within the normal range. All of his three siblings have similar symptoms, such as severe mental retardation and elevated CK level in the serum (1735-3641 IU/L) and lack apparent muscular weakness. Gene analyses by multiplex PCR and Southern blotting showed all of the siblings had the deletion of exon 4 in the dystrophin gene. Pathological findings of a muscle biopsy specimen showed a mild irregular dystrophin stain of the muscle surface membrane. This is a rare familial case of Becker muscular dystrophy manifesting severe mental retardation with scarce muscular weakness.

[A case of esophageal achalasia followed by Parkinson's disease].

In 1992, a 63 year-old woman complained of dysphagia and chest pain, and was diagnosed with esophageal achalasia. Three years later, she developed resting tremor, cog-wheel rigidity, and retro-pulsion, and was diagnosed with Parkinson's disease and given appropriate medication. Several years later, intractable vomitting and aspiration pneumonia developed, and the lower esophageal sphincter was dilated using a pneumatic balloon dilator under gastroscopic guidance in 2004. That procedure improved her symptoms and the esophageal dilation was visualized on chest CT images. Herein, we report this rare case of esophageal achalasia followed by Parkinson's disease and discuss the relationship between the two diseases.

Subacute bulbar palsy as the initial sign of follicular thyroid cancer.

We report a 64-year-old woman with follicular thyroid cancer found by subacute bulbar palsy. Progressive bulbar palsy (PBP) was considered the most likely diagnosis, because no abnormal finding was detected on brain CT and blood test except for the decrease of free T4. An echogram of the thyroid revealed a small nodule which was shown to be class IIb by fine needle biopsy. However, 201Tl scintillation examination showed skull base metastasis. Follicular thyroid cancer sometimes seems to manifest as a distant metastasis with no clinically evident thyroid lesion. This case suggested the importance of a detailed survey for malignancy, when subacute bulbar palsy is seen.

Two types of VIP neuronal components in rat suprachiasmatic nucleus.

Vasoactive intestinal peptide (VIP) neurons constitute a large group in the suprachiasmatic nucleus (SCN) and it is thought that they are involved in the generation and entrainment of circadian rhythm. We have characterized these VIP-expressing neurons in rat SCN by their ability to induce the mammalian Period1 (Per1) gene in response to light exposure, innervation of retinal afferents, day-night variations in VIP mRNA, and coexpression of gastrin releasing peptide (GRP). VIP neurons in the ventrolateral SCN (SCNVL) were subdivided into two groups, light-evoked Per1-inducible main SCNVL (SCNVLmain) and non-Per1-inducible medially located SCNVL (SCNVLmed). Retinal innervation was abundant in the SCNVLmain but nearly absent in the SCNVLmed. Day-night variation in VIP mRNA expression level was observed in the SCNVLmain but not in the SCNVLmed. GRP mRNA was seen in rarely SCNVLmed but abundant in SCNVLmain, where some neurons coexpressed VIP mRNA. These findings indicate that VIP neurons in the SCN can be divided into two topographically and functionally distinct groups.