Congenital muscular dystrophy (CMD) refers to a heterogeneous group of muscular dystrophies with onset during the neonatal period. Among them, some types of CMD are characterized by the association of brain malformations and ocular abnormalities. Biochemical analyses revealed altered glycosylation and decreased laminin-binding activity of α-dystroglycan in these disorders, therefore they are correctively called α-dystroglycanopathy. Recently, mutations in the genes encoding demonstrated or putative glycosyltransferases have been identified in α-dystroglycanopathy. Fukuyama-type CMD and MDC1C are caused by mutations in the fukutin and fukutin-related protein (FKRP) genes, respectively. Mutations in the protein O-mannose β-1, 2-N-acetylglucosaminyltransferase (POMGnT-1) and protein O-mannosyltransferase 1 and 2 (POMT1 and POMT2) genes cause muscle-eye-brain disease and Walker-Warburg syndrome, respectively. In addition, mutations in Large gene results in MDC1D. Furthermore, recent genotype-phenotype correlation analyses have revealed that the spectrum of phenotypes caused by mutations in these genes is much wider than originally assumed. In this review, we focus on the molecular pathomechanism and diverging clinical phenotypes of α-dystroglycanopathy.
Epilepsy is a chronic neurological disorder that affects one million people in Japan. Medical treatment is highly effective for this disorder. The antiepileptic treatment brings 70% of the patients to seizure freedom. Current guidelines recommend carbamazepine for partial (focal) seizures and valproate for generalized seizures as the first-line drug; however, indivizualized drug selection in accordance to the patients' condition is mandatory. Modern antiepileptic medications have better tolerability and less dug-to-drug interaction, and some of them are waiting to be approved in Japan. Special attention is necessary for the care of woman in child-bearing age, adolecents, and elderly persons. Advances of surgical treatment of the epilepsy brought many medically intractable patients to be seizure free. Early identification of the surgical candidate is an important task for clinicians.
To investigate the current state of education for undergraduates, the subcommittee of the Japanese Society of Neurology for undergraduate education sent a questionnaire on the 2001-version of Model Core Curriculum to the department of neurology in 80 medical universities and their 7 associate medical institutes throughout Japan. Answers were obtained from 56 out of those 87 institutes (64.4%). According to the answers, the Core Curriculum was introduced to the program of undergraduate education in 93% of those 56 universities. For the revision of neurology part in the current Core Curriculum, there are number of requests for improving the description on the neurological examination, list of common symptoms and disorders, and addition of therapeutics. Despite application of the Model Core Curriculum in medical education, the present study disclosed that there were considerable difference in the number and content of the lectures, and the duration of clinical clerkship in neurology ward. These differences of the curriculum and training program depends on not only the number of staffs, but also whether they are working as staffs in a department of neurology or as a small group of neurologists within a department other than neurology.
We studied the incidence and clinical characteristics of pseudogout complicating stroke and the clinical characteristics of pseudogout occurring after stroke. Ten of 181 patients with stroke developed pseudogout. Compared with the patients of other disease, the incidence of pseudogout in the stroke patients was significantly high. Age at onset was 75 to 90, with a mean of 82. The time interval from stroke to onset of pseudogout ranged from 3 to 31 days, with a median of 5.5 days. The most common initial symptom was fever (90%), whereas subjective arthralgia was not highly frequent (50%). The affected joints were the knee in 6, wrist in 5, shoulder in 2, elbow in 2, atlantoaxial (crowned dens syndrom) in 2 and ankle in the remaining one. All patients developed pseudogout either on the paretic side or on atlantoaxial joint when their condition required extended bed-rest or limited their mobility. All the patients had elevated CRP levels (mean CRP 12.0mg/dl). Our findings suggest that this under-recognized disease should be noted as one of the complications after stroke.
We describe an autopsied case of an 86-year-old woman who presented with acute tetraparesis, bulbar palsy, and respiratory insufficiency. MRI showed a T2 hyperintensity lesion in the medulla oblongata and C1 and C2 level cervical cord, and an unruptured aneurysm in the left posterior inferior cerebellar artery. With an initial diagnosis of Bickerstaff's brainstem encephalitis, we started corticosteroid therapy. Initially, the corticosteroid treatment gradually improved her general condition; however, about two weeks later she died of an acute respiratory insufficiency. From the postmortem pathological examination, we considered a venous circulatory disturbance of the medulla oblongata and upper cervical cord. No arteriovenous shunt was found in the intramedulla and the medulla oblongata was partially compressed on the left side by an unruptured aneurysm. However, neither inflammatory nor malignant cells were found in the lesion. What caused the venous circulatory disturbance was unclear, but the dural arteriovenous fistula could have been responsible. Our case suggested that venous circulatory disturbances accompanied with an aneurysm need rapid consideration by angiography followed by intervention.
A 67-year-old woman developed gait disturbance, dysarthria, cognitive impairment and incontinence at age 65, and became bedridden. She showed mutism, stupor and lower limb spasticity. Cranial CT and MRI revealed marked ventricular enlargement and a cerebellopontine angle tumor. CSF study showed normal pressure (125mmH2O) and elevated protein (143mg/dl). Radionuclide cisternography showed redistribution of radionuclide to the ventricles and intraventricular residual radionuclide after 72 hours, which allowed a diagnosis of normal pressure hydrocephalus. After removal of the tumor, ventricle size and CSF protein decreased, and the symptoms of cognitive impairment and motor dysfunction resolved. Histological examination showed acoustic neurinoma. Over the half of hydrocephalus following acoustic neurinoma shows a tendency to improve by surgical resection of the tumor. Neurologists who see cognitively impaired spastic bedridden patients should not overlook this pathology.
We report a rare case of multiple cranial nerve palsy associated with pregnancy, the cause of which remained to be clarified despite of extensive inspections. A 28-year-old woman with type 1 diabetes on insulin therapy developed left oculomotor nerve palsy in the fourth month of pregnancy. Her symptoms improved after one month's administration of vitamins B1 and B12. Numbness appeared in the left side of the face in the 8th month of pregnancy, and then moved to the right side in two weeks. Dysarthria and dysphagia occurred one month later. Bulbar symptoms were worsened, and she became unable to eat or drink. Neurological examination revealed disturbance of sensation in the right side of the face, soft palate paresis, and bilateral atrophy and fasciculation of the tongue. Extensive laboratory examinations including immunological and endocrinological studies, cerebrospinal fluid examination and brain magnetic resonance imaging were unremarkable. These symptoms remitted spontaneously after delivery, and the methylprednisolone pulse therapy accelerated the improvement. Neurological examination done one year after delivery showed complete recovery of the symptoms except for persistent tongue atrophy.