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.

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.

[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.

[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.

[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.

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.

Primary skeletal muscle involvement in chorea-acanthocytosis.

Chorea-acanthocytosis (ChAc) is a hereditary disease characterized by involuntary movements and amyotrophy with elevation of serum creatine kinase. Although skeletal muscle involvement in ChAc has been suggested, the mechanism remains unclear. To investigate chorein abnormalities of the skeletal muscles of ChAc patients with an apparently heterozygous VPS13A mutation compared with those of other hereditary choreic diseases, we performed histological and immunohistochemical studies of the skeletal muscles from 3 ChAc, 1 Huntington's disease (HD), 1 McLeod syndrome (MLS), and 1 normal control (NC) with 2 originally generated anti-chorein antibodies. Chorein immunoreactivities in HD, MLS, and NC were found linearly along the sarcolemma and appeared as speckles in the sarcoplasma, but those in ChAc were uneven and discontinuous along the sarcolemmas and increased in the sarcoplasma especially in type I fibers. This histological observation suggests chorein abnormalities of skeletal muscles might be associated with primary involvement of skeletal muscles in this disorder.

Neurological deficits are associated with increased brain calcinosis, hypoperfusion, and hypometabolism in idiopathic basal ganglia calcification.

We report two familial cases of idiopathic basal ganglia calcification. A 60-year-old proband with choreoathetosis, dysarthria, and cognitive decline showed more extensive brain calcinosis, hypoperfusion, and hypometabolism than did his asymptomatic 82-year-old mother. The mother had no frontal lobe calcinosis but basal ganglia and dentate nucleus depositions were detectable. Perfusion neuroimaging, however, was normal in the asymptomatic mother and abnormal in the clinically impaired proband. The presence of calcinosis cannot be used as an index of neurological impairment but the extent of calcinosis and reduction in perfusion and metabolism may be useful for separating symptomatic from asymptomatic subjects with IBGC. These findings suggest that an interruption of neuronal circuitry may cause neurological deficits. The degree of neurological deficits may correlate with the severity of calcinosis and the reduction of perfusion and metabolism.

[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.

Induction of humoral responses specific for paraneoplastic cerebellar degeneration-associated antigen by whole recombinant yeast immunization.

Paraneoplastic cerebellar degeneration (PCD) is a potent autoimmune disorder in which antigen-driven responses toward the onconeural antigen are assumed to occur in patients. Yeast cell wall has adjuvant capacity and provides immunostimulatory effects of the antigen expressing in viable cells. The recombinant yeast expressing the PCD-associated antigen may become an immunogen for inducing PCD-associated autoimmunity in mice. We attempted to induce autoimmune responses with whole recombinant yeast expressing PCD-associated antigen. SJL/J strain of mouse is found to be a responder to the major epitope on the antigen for anti-Purkinje cell antibodies, and whole recombinant yeast could induce cellular and humoral autoimmune responses in vivo ion SJL/J mice. The immunization technique based on the recombinant yeast expressing a PCD-associated antigen provides a new tool for analyzing the underlying immunological pathomechanisms of PCD.