Follow-up study of a patient with early onset cerebral amyloid angiopathy following childhood cadaveric dural graft.

We retrospectively studied the T2 star (T2*)-weighted magnetic resonance imaging (MRI) of a 40-year-old patient diagnosed with symptomatic early-onset cerebral amyloid angiopathy (CAA), occurring 34 years following childhood neurosurgery using a cadaveric dural patch. Our findings revealed that CAA associated with cadaveric dural transplantation could progress rapidly, sometimes with bilateral bleeding. This microbleed evolution is suggestive of water-soluble amyloid-ß transmission via cerebrospinal fluid alongside perivascular drainage pathways with deposition in the cerebral artery walls due to clearance disturbances. Multiple intracerebral hemorrhages associated with CAA with a childhood cadaveric dural graft should be considered a life-threatening medical complication.

Moyamoya disease presenting with an acute confusional state in an elderly patient.

Moyamoya disease is the angiographic diagnosis of a clinical syndrome showing bilateral stenosis or occlusion of the distal internal carotid arteries and their major branches with extensive parenchymal, leptomeningeal, or transdural anastomoses. The clinical features normally present as reversible ischemic neurologic deficits, sensory-motor attacks with acute hemiplegia, and motor convulsion. An acute confusional state (ACS) among hospitalized patients is a frequent and serious problem. It is characterized by an acute neurologic deficit with a fluctuating course of impaired attention span, unorganized thinking, and altered levels of consciousness. We report a case of 66-year-old woman who presented with an ACS in the emergency department. The subsequent workups including a neuroradiological examination revealed a rare case of moyamoya disease with bifrontal ischemic infarction. The recognition of an ACS as a manifestation of moyamoya disease should therefore be included in the differential diagnosis of elderly patients who present with an acutely altered neuropsychiatric state. A prompt diagnosis may help to select the most appropriate therapy for this rare disorder especially in elderly patients.

A neuropathological study of autosomal-dominant chorea-acanthocytosis with a mutation of VPS13A.

We report the first autopsy case of genetically confirmed, autosomal-dominant chorea-acanthocytosis (AD-ChAc), showing a heterozygous mutation (G-A) at nucleotide position 8,295 in exon 57 of VPS13A. The patient was a 36-year-old Japanese man and the duration of his illness was 11 years. Neuropathologically, the patient showed marked atrophy and neuronal loss, particularly small and medium-sized neurons, with astrocytic gliosis in the caudate nucleus, putamen and globus pallidus. These findings were similar to previous autopsy reports of autosomal-recessive ChAc (AR-ChAc) with mutations of VPS13A. The broad distribution of atrophic neurons and astrocytosis throughout the whole brain was unique in our AD-ChAc patient and has not been described in AR-ChAc. The neuronal density of the dorsal caudate nucleus was lower than that of the ventral side in this patient as well as in three Huntington's disease (HD) patients. The neuronal densities in both the rostral and caudal sides were lower than that in the middle region at the anterior commissure level, while in the three HD patients, the neuronal densities of the caudate nucleus were more decreased in the caudal side. This ChAc patient showed faint immunoreactivity in the caudate nucleus and globus pallidus with antibodies against the striatal neurotransmitters, methionine-enkephalin, leucine-enkephalin and substance P. The difference in patterns of neuronal vulnerability could reflect those in the mechanisms of neurodegeneration between ChAc and HD.

Vestibular symptoms in acute hemispheric strokes.

A prospective study focused on whether vestibular symptoms are seen in acute hemispheric strokes, and if so, the frequency and lateralization of causative lesions on MRI. Among 668 patients with hemispheric infarction, we prospectively included those with chief complaints of acute vestibular symptoms, such as vertigo/dizziness, nausea/vomiting and gait instability, in the "VS" group. We also retrospectively reviewed MRI of all stroke patients, and included cases with the findings of parieto-insular vestibular cortex (PIVC) or temporo-periSylvian vestibular cortex (TPSVC) lesion by diffusion-weighted MRI, in the "PIVC" group. Eight patients were found to belong to the VS group, and six other patients to the PIVC group. In the VS group, six patients had the responsible lesion on the right hemisphere, in the middle cerebral artery (MCA) territory except one case and two on the left MCA territory, particularly in the insula, retro-insular region, superior/middle temporal gyrus, angular gyrus, supra-marginal gyrus, putamen and hippocampus/para-hippocampal gyrus. In contrast, none of the six other patients of the PIVC group had vestibular symptoms. One of them had a lesion in the right hemisphere and five in the left hemisphere. Four lesions were located in the insular area and two within the temporal lobe. In conclusion, cerebral hemispheric infarction limited to the PIVC or TPSVC does not necessarily cause vertigo. However, unilateral hemispheric infarctions, restricted to the areas belonging to the vestibular cortical network may cause vestibular symptoms. The lesions responsible for vestibular symptoms are located more often in the right hemisphere.

[Cerebellar Control of Ocular Movements: Application to the Topographical Diagnosis of Cerebellar Lesions].

Over the last decade, substantial information on cerebellar oculomotor control has been provided by the use of sophisticated neuroanatomical, neurophysiological, and imaging techniques. We now know that an intact cerebellum is a prerequisite for normal oculomotor performance. This review clarifies the current knowledge on structure-function correlations of the cerebellum in relation to ocular movements and allows them to be applied to topographical diagnosis of cerebellar lesions. The cerebellar regions most closely related to oculomotor function are: (1) the flocculus/paraflocculus for VOR suppression, cancellation, smooth pursuit eye movement and gaze-holding, (2) the nodulus/ventral uvula for velocity storage and low frequency prolonged vestibular response, and (3) the dorsal oculomotor vermis (declive VI, folium VII) and the posterior portion of the fastigial nucleus (fastigial oculomotor region) for saccades and smooth pursuit initiation. Symptomatically, defects in the flocculus/parflocculus cause saccadic pursuit, downbeat nystagmus, and impairments to visual suppression of the VOR. Lesions of the nodulus/uvula reveal as periodic alternating nystagmus. Lesions of the oculomotor vermis and the fastigial nucleus can induce saccadic dysmetria, while fastigial nucleus lesions may also cause ocular flutter/opsoclonus. A detailed knowledge of cerebellar anatomy and the physiology of eye movements enables localization of lesions to specific areas of the cerebellum.

Binding of the ELAV-like protein in murine autoimmune T-cells to the nonameric AU-rich element in the 3' untranslated region of CD154 mRNA.

The CD154 molecule is important for experimental allergic encephalomyelitis (EAE) which is mediated by autoimmune CD4(+) T-cells. Post-transcriptional instabilization/stabilization of mRNAs, which contain an adenylate uridylate rich element (ARE) in their 3' untranslated region (3'UTR), is regulated in part by binding of ARE-binding proteins to the element. We have investigated the protein which binds to the nonameric ARE in the 3'UTR of CD154 mRNA. A protein which binds to the CD154 ARE was found to exist in a extract prepared from murine autoimmune T-cells activated with myelin basic protein (MBP), and turned out to be mHuR which is a ubiquitous ELAV-like protein. It was found that mHuR was upregulated upon stimulation of the T-cells with a MBP antigen. The CD154 ARE and the ARE in the 3'UTR of tumor necrosis factor-alpha (TNF-alpha) mRNA were competed in binding to mHuR, indicating that both AREs bind to the same site on mHuR. The presence of the CD154 ARE downstream of the luciferase cDNA in a reporter plasmid decreased the translational efficiency, and co-expression of the mHuR slightly increased the translation. These results suggest the possibility that the ELAV-like protein participates in the regulation of the expression of CD154 on the autoimmune T-cells. Modification of the expression of CD154 on autoimmune T-cells by regulating the ELAV-like protein may provide effective therapy for EAE and human multiple sclerosis.

[Ictal alteration of 99mTc ECD SPECT imaging in a patient with secondary paroxysmal kinesigenic dyskinesia caused by hyperglycemia].

We described a 61-year-old man with diabetes mellitus who presented with hyperglycemia related paroxysmal kinesigenic dyskinesia (PKD) with sudden development of paroxysmal unilateral involuntary movements (IMs) of his neck and the left extremities. Ictal 99mTc-ethylcysteinate dimer SPECT (ECD-SPECT) revealed a hyperperfusion over the contralateral frontal cortex and a hypoperfusion over the contralateral basal ganglia. Immediate correction of hyperglycemia after admission resulted in a marked improvement of IMs and a return to normal cerebral blood flow on interictal ECD-SPECT imaging. These findings suggest that dysfunction of the indirect pathway through the basal ganglia lead to an imbalance of the cortico-striato-thalamo-cortical circuit and may have contributed to the cause of PKD in this case.

[The Barrés test and Mingazzini test -Importance of the original paper by Giovanni Mingazzini].

In order to find a subtle hemiparesis of the arms and legs, so called "Barré's test" has been routinely used in clinical practice. This eponym has been questioned by several neurologists. To clarify this, I searched and found the original paper by Giovanni Mingazzini, reported in Revue Neurologique in 1913. He showed arm drift test with his original photo, as asking the patient to stretch his arms in front, hands in the same horizontal plane with the manner of swearing and the fingers spread. The eyes are closed. The examiner observes downward drift of the hand after one half to a minute. He described a similar test for the legs in this article. The patient in supine position raises the legs in a 45 degree angle from the bed. If the leg drops downward too early, an organic hemiparesis could be present. Barré described a new leg drift test in 1919 with a patient lying on the abdomen. He also presented the Mingazzini's arm and leg tests with photos as carried by his patient-models in his article of 1937. He did not quote the original article of Mingazzini as a reference. These brought us incorrect information to consider the presence of Barré's arm test.

[Ring (20) chromosome epileptic syndrome].

Ring (20) chromosome epilepsy syndrome is characterized by highly refractory epilepsy that is often associated with non-pathognomonic, electroencephalographic (EEG) changes. Seizures typically begin during the stage of childhood around the age of 6 years. Nonconvulsive status epilepticus (NCSE) is the most common seizure types and is distinguished by a long-lasting, confusional state that is often associated with EEG patterns in the form of prolonged, high-voltage slow waves with occasional spike/sharp components. Patients with this syndrome suffer from intractable seizures with cognitive decline and frequent epileptic episodes. Accompanying features of this rare disorder, such as superficial minor dysmorphic abnormalities if any, mental retardation and behavioral changes are quite variable. Because of the variability in clinical presentation, in particular the lack of clear dysmorphic features, the clinical diagnosis of this disorder can be delayed before being diagnosed genetically. Most patients with this syndrome have chromosomal changes in the form of a mosaic. High levels of mosaicism correlate well with a lower age of onset and severe cognitive impairment. Here, we emphasize the importance of early G-banding chromosomal analysis when patients present with unexplainable severe seizures and repetitive NCSE, even in the absence of any dysmorphic features suggestive of a chromosomal disorder.

Cardiac 123I-MIBG scintigraphy can assess the disease severity and phenotype of PD.

OBJECTIVE: Cardiac (123)I-metaiodobenzylguanidine (MIBG) scintigraphy studies of patients with idiopathic Parkinson's disease (PD) found decreased uptake. Whether this decrease is associated with clinical severity as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS) and the phenotypes of PD has not been determined. METHODS: Cardiac MIBG scintigraphy was performed on 34 patients with PD, 7 with multiple system atrophy (MSA), 4 with dementia with Lewy bodies (DLB), and 11 normal controls (NCs). Early and delayed MIBG heart/mediastinum (H/M) ratios were evaluated. PD severity was assessed by the Hoehn and Yahr (H-Y) stage and UPDRS. Patients were grouped in two phenotypes, tremor and postural instability gait difficulty (PIGD)-dominant groups based on UPDRS components. Associations between MIBG uptake and age at onset, UPDRS, and disease phenotype were analyzed in each group. RESULTS: The early H/M ratio was significantly lower in patients with PD (1.45+/-0.207) than in the NCs (2.08+/-0.231), and in those with MSA (1.99+/-0.284), but not in those with DLB (1.29+/-0.0435). The delayed H/M ratio for PD (1.33+/-0.276) also was significantly decreased as compared to the ratios for NCs (2.17+/-0.286) and MSA (2.16+/-0.414) but not DLB (1.16+/-0.0949). The early H/M ratio was significantly correlated with both UPDRS score and age at onset, whereas the delayed H/M ratio only was significantly correlated with age at onset. The PIGD-dominant group had significantly higher UPDRS scores and lower H/M ratios than the tremor-dominant group. CONCLUSION: Cardiac MIBG scintigraphy can be used to differentiate PD from MSA and NC, and to determine the disease severity and phenotypes of PD.

[A questionnaire survey of the neurology training program in Japan].

A questionnaire survey was performed in order to see the current trends of the neurology training program in Japan. A questionnaire was sent out to 81 neurology program directors of the medical schools and large hospitals. 72 program directors answered the questionnaires. According to the summed results, each program had an average of 37 inpatient beds, 7 teaching staffs with the neurology board certification. The program had an average of 4 residents annually, and they served as junior neurology residents for 1.8 years, and as chief residents for 1 year with 6 months of hospital consultation. 1.4 years training in the internal medicine was prerequisite for the neurology program. The training of clinical neurophysiology was done mainly by the own faculty staff in each program, but the training of neuroradiology and neuropathology varied. A quarter of the training programs had their own teaching staffs of neuroradiology and the rest of three quarters asked for training to the neuroradiology department. 32 of 72 programs had their own teaching neuropathologists and 26 programs asked the training in the pathology department and 14 programs did not have any teaching staffs of neuropathology. It seems that these numerical data are quite similar to those of the American standard of Accreditation Councils. We must still improve the real contents of the neurology training program with more capable teaching staffs.

[A case of Gitelman's syndrome presenting with the hypokalemic periodic paralysis].

We report a rare case of Gitelman's syndrome (GS) presenting with the hypokalemic periodic paralysis. A 27-year-old man was admitted to our hospital because of transient weakness of the limbs. Past history was unremarkable, including the delivery and early developmental milestones, except for a transient limb weakness 7 times since the age of 15 years. The blood pressure was 140/90 mmHg. The physical examinations were unremarkable. Neurologically, the patient was fully oriented. The cranial-nerve functions were intact. Manual muscle tests revealed 1/5 weakness in his neck and extremities. Sensation was normal in all modalities. The deep tendon reflexes were present but decreased mildly. Laboratory tests showed hypokalemia (1.9 mEq/l), hypomagnesemia (1.8 mEq/l), and hypocalciuria (40.0 mg/dl). Plasma rennin activity and aldosterone concentration were elevated. The molar ratio of urinary calcium/creatinine was 0.11 (< 0.2). Arterial blood gas showed mild metabolic alkalosis with respiratory compensation. Because of these data, the diagnosis of GS was made. Gene mutations in the renal thiazide sensitive Na-Cl cotransporter (TSC) have already been shown to cause GS. Although we searched for gene mutation of TSC, none of 25 mutations in 18 out of 26 exons which had been previously reported were found. This is the first report of Gitelman's syndrome presenting with the hypokalemic periodic paralysis in Japan.

[A case of portal-systemic shunt encephalopathy due to congenital portal vein hypoplasia presenting with abnormal cerebral white matter lesions on the MRI].

A 49-year-old woman, without any past history of liver diseases and blood transfusion, was admitted to our service because of somnolence, and flapping tremor. Neurologically, she was drowsy and disoriented. She had bilateral pyramidal tract signs and flapping tremor. Although the laboratory examination showed marked hyperammonemia (217 micrograms/dl), neither abdominal CT nor liver biopsy showed any evidence of liver cirrhosis. An abdominal angiography showed portal vein hypoplasia associated with the portal-systemic shunt. A T2-weighted MRI showed the high intensity areas in the bilateral deep cerebral white matter, and the posterior limbs of the bilateral internal capsules. This is a rare case of portal-systemic shunt encephalopathy due to congenital portal vein hypoplasia presenting with abnormal cerebral white matter lesions on the MRI.

[Sir William Richard Gowers: author of the "bible of neurology"].

William Richard Gowers is one of the great pioneers in neurology and the author of the well-known neurology textbook, "A Manual of Diseases of the Nervous System." His concepts of neurology are based on meticulously and carefully accumulated knowledge of history, observations, and neurological examinations of patients with various neurological diseases. He is not only a great neurologist but also a great teacher who loves teaching students and physicians through well-prepared lectures. We can glean the essence of the field of neurology through his life story and numerous writings concerning neurological diseases.

[An overview of epilepsy: its history, classification, pathophysiology and management].

Epilepsy, a common chronic set of neurological disorders characterized by seizures, affects more than 50 million people worldwide. In fact, it is estimated that the annual incidence of new onset epilepsy in the general population is more than 80 per 100,000, occurring mostly in children and the elderly. Epilepsy is not a single specific disease, or even a single syndrome, but rather a broad category of symptom complexes arising from any number of disordered brain functions. The history of epilepsy dates back to a time when it was associated with religious experiences and even demonic possession; textbooks from the Babylonian Era (718-612 BC) emphasize the supernatural nature of epilepsy, while in ancient Greece, Hippocrates described it as the "Sacred Disease". Our modern understanding of epilepsy as a neurological disorder associated with seizures only originated in the mid-19th century through the research of John Hughlings-Jackson. Classification of epilepsies, epileptic syndromes, and related seizure disorders first appeared 1981 and later in 1989, as described by the International League Against Epilepsy (ILAE). Newer classifications have since been proposed by the same organization; however, these are still rather controversial and have not yet been accepted worldwide. The pathophysiology of epilepsy, including the pharmacological and neurophysiological aspects, has been studied extensively. Epileptogenicity is induced by abnormal cellular excitability that arises from depolarization and hyperpolarization events, as well as from aberrant neuronal networks that develop abnormal synchronization. These events can be studied using mutant epileptogenic animals, such as the GAERS rat model of absence epilepsy. The past 15 years has seen the development of many new drugs for the treatment of epilepsy, thus providing a diverse choice for epileptologists and their patients. However, a better understanding of these drugs is required to improve the therapeutic management of patients suffering with the chronic burden of epilepsy.

Serious adverse effects of gamma knife radiosurgery for mesial temporal lobe epilepsy.

Gamma knife radiosurgery (GKRS) for mesial temporal lobe epilepsy (MTLE) has been proposed as an alternative to surgical resection. We report serious adverse effects of the treatment after follow-up periods over 9 years in 11 patients treated with GKRS between 1997 and 2000. The target volume of the entorhinoamygdalohippocampectomy area was 4.8-17.1 ml. Marginal dose of 20-25 Gy to the 50% isodose was delivered. One patient was drowned after suffering seizure 7 months after GKRS. Two patients did not show any reduction in seizure frequency over 9 and 18 months. Both patients requested open surgery and became seizure-free postoperatively. Four of the other eight patients were classified as Engel's class I within 4 years after GKRS. One of the four patients experienced symptomatic radiation-induced cerebral edema transiently, one developed radiation necrosis and required surgery 5 years after GKRS, and one developed cognitive impairment with hemiparesis 10 years after GKRS. Magnetic resonance (MR) imaging showed a large cyst in the irradiated temporal lobe. This patient recovered fully after the cyst excision. Only one patient became seizure-free and antiepileptic drug-free without symptomatic radiation-induced complications. However, MR imaging revealed abnormal enhancement, cyst formation, and diffuse white matter change in the irradiated temporal lobe 9 years after GKRS. GKRS for MTLE causes adverse effects of delayed seizure remission and symptomatic radiation-induced complications. Therefore, GKRS cannot be considered as an ideal alternative to surgery for MTLE. Long-term follow-up studies including MR imaging with contrast medium are required for the patients even after successful control of seizures.

[Overview: diagnosis of vestibular syndromes].

Vestibular syndromes are one of the commonest paroxysmal disorders in our clinical practice. These consist of vertigo, oculomotor abnormalities (nystagmus), postural changes and nausea/vomiting. Vertigo can be classified as real vertigo and dizziness, based upon the presence of clinical rotatory perception. In order to diagnose a responsible lesion for various central and peripheral vestibular syndromes, we have to carefully observe nystagmus in patients with acute vertigo. Gaze-evoked nystagmus is the most important nystagmus in patients with the central vestibular syndromes. The finding is easily found at the bed side examination. In order to keep a velocity-position neural signal such as gaze holding, the neural structure to hold and maintain the neural command for a saccade is hypothesized and this has been called as the brainstem neural integrator, which sends tonic-step commands for eccentric gaze. If this fails then the integrator becomes leaky and the eyes drift back to the central position. This movement necessitates corrective saccades, hence gaze-evoked nystagmus will ensue. Vertical nystagmus such as primary position upbeat or downbeat nystagmus is also seen only in the central vestibular syndromes. The detection and diagnosis of these characteristic nystagmus are essential for primary clinicians who care patients with acute vertigo.