Familial adult-onset Alexander disease with a novel mutation (D78N) in the glial fibrillary acidic protein gene with unusual bilateral basal ganglia involvement.

In this report, we describe the case of a new Japanese family (32 to 64 years old; 2 females and 1 male) affected by adult-onset Alexander disease. Clinically, one member (age at onset, 56 years old) developed cerebellar ataxia, another (age at onset, 55 years old) showed cerebellar ataxia and pseudobulbar signs, and one member (32 years old) was asymptomatic. Marked atrophy of the medulla oblongata and spinal cord was detected in the two symptomatic patients by magnetic resonance imaging (MRI). However, in the asymptomatic patient, cervicomedullary atrophy was mild. Hyperintensity signals in the medulla oblongata were detected in the two symptomatic patients, but not in the asymptomatic patient. In addition, there are symmetrical hyperintensity signals in the posterior part of the globus pallidus on T2-weighted images in the two symptomatic patients, which are rarely observed in adult-onset Alexander disease. Molecular genetic analysis revealed a novel missense mutation (p. D78N) in the glial fibrillary acidic protein (GFAP) gene in this family. The typical atrophy of the medulla oblongata and upper cervical cord detected by MRI is the diagnostic feature of adult-onset Alexander disease. Genetic analysis of the GFAP gene is recommended for all patients with late-onset progressive ataxia and suspected of having adult-onset Alexander disease on the basis of MRI findings. Additionally, these characteristic MRI patterns might even lead to the identification of asymptomatic cases, as in one of our cases.

A patient with splenic marginal zone lymphoma presenting with spastic paraplegia as the initial symptom.

In this report, we describe the case of a patient with splenic marginal zone lymphoma (SMZL) who presented with spastic paraplegia as the initial symptom. A 42-year-old male developed progressive spastic paraplegia over 4 months. His neurologic examination revealed paraplegia with pyramidal syndrome, hypoesthesia below the T1 level, and anal hypotonia. Magnetic resonance imaging (MRI) of the spinal cord revealed an extensive high-intensity signal in T2-weighted sequences and swelling involving the thoracic region and conus medullaris. A laboratory test revealed presence of the serum M component. Abdominal computed tomography images showed moderate splenomegaly. Abnormal lymphocytes of B-cell lineage markers (CD19+, CD20+, and CD25+; surface immunoglobulin κ expression; IgD+ and IgM+) were found in the peripheral blood, cerebrospinal fluid, bone marrow and spleen. Splenectomy confirmed the SMZL diagnosis. After the completion of chemotherapy, the patient was in complete remission, and spinal MRI findings were normal. Intramedullary spinal cord involvement in SMZL is extremely rare, and, to the best of our knowledge, this is the first case of SMZL with intramedullary spinal cord involvement associated with clinical and radiologic signs without the involvement of cerebral structures. Spastic paraplegia can be the initial presentation of SMZL.

Hypoperfusion of the motor cortex associated with parkinsonism in dementia with Lewy bodies.

OBJECTIVE: This study aimed to investigate the impact of parkinsonism on regional cerebral blood flow (rCBF) in dementia with Lewy bodies (DLB). METHOD: Forty-four probable DLB patients, comprising 13 patients without parkinsonism and 31 patients with parkinsonism, and 16 normal controls were selected for this study. We evaluated the rCBF in each group by means of N-isopropyl-p-[(123)I] iodoamphetamine (IMP) and single photon emission computed tomography (SPECT). The rCBF in the different groups was compared using voxel-by-voxel Statistical Parametrical Mapping (SPM). RESULT: Patients with DLB showed low rCBF in the frontal, temporal, and occipital cortex with relative sparing of the paracentral region. DLB patients with parkinsonism (DLB-P) had lower rCBF in the primary motor cortex (M1) and left supplementary motor area (SMA) than DLB patients without parkinsonism (DLB-nonP). DLB-nonP patients showed decreased rCBF in the left temporo-occipital region. CONCLUSION: This study suggests that two distinct clinical entities are involved in DLB. In addition, CBF changes in the M1 and SMA are seen in the early stages of Parkinson's disease. This result would help in diagnosing DLB in the context of Lewy body (LB) disease.

Isolated astasia in acute infarction of the supplementary-motor area.

Astasia, which is the inability to stand in the absence of motor weakness or marked sensory loss, is an uncommon clinical feature of stroke in the thalamic ventrolateral region. The authors describe a patient with a unilateral supplementary motor area (SMA) infarction presenting with contralateral astasia. On neurological examination, he would lean to the left side and would fall unless supported. He showed no muscle weakness, sensory deficits or cerebellar ataxia. Magnetic resolution imaging of the brain showed acute infarction only involving the right SMA. On the basis of the anatomy that the SMA is connected to the vestibulocerebellar system through the ventrolateral nucleus of the thalamus, the authors concluded that contralateral astasia probably resulted from disruption of this connection following infarction of the SMA.

[Body lateropulsion as the main symptom of pontine vascular disease--comparison with lateral medullary vascular disease].

Lateropulsion of the body is rarely encountered as an isolated or predominant manifestation of pontine cerebrovascular disease. We compared 2 cases of pontine vascular lesions with 3 cases of lateral medullary infarction; all the patients had presented with body lateropulsion. The patients with pontine lesions tended to full on the side contralateral to the lesion,whereas the patients with lateral medullary infarction, fell on the ipsilateral side. Lateropulsion itself improved within 1 or 2 weeks in all the patients. The pontine lesion was localized to the paramedian tegmentum, just ventral to the fourth ventricle, while the medullary infarction was localized to the lateral surface of the medulla oblongata. The present findings support the possibility that body lateropulsion in patients with pontine vascular lesion is attributed to lesions in the graviceptive pathway that ascends through the paramedian pontine tegmentum.

Hepatitis B virus-related vasculitis manifesting as severe peripheral neuropathy following influenza vaccination.

We report the case of a 68-year-old man who developed hepatitis B virus (HBV)-related vasculitis, manifesting as mononeuritis multiplex, 8 days after influenza vaccination. The patient was a carrier of wild-type HBV, and had never received influenza vaccination. Histologic examination of the left sural nerve revealed necrotising vasculitis predominantly involving small blood vessels. HbsAg deposits were observed at a high density around the epineurial blood vessels of the sural nerve. He was treated with prednisone and Lamivudine. His condition improved gradually. However, seroconversion of HBs and HBe Ag was not detected. At the last follow-up 2 years later, his vascilitis did not recur. On the basis of the time of onset of vasculitis, the presumptive immune-mediated pathology of this disorder suggests a possible etiologic link with influenza vaccine. To our knowledge, our case is the first to show vasculitis of peripheral nerves proven pathologically after influenza vaccination.

Delirium in two patients with Bickerstaff's brainstem encephalitis.

In this report, we describe the case of two patients with Bickerstaff's brainstem encephalitis (BBE) who developed delirium manifested as emotional incontinence, restlessness, and aggressive behavior from disease onset. Serum anti-GQ1b and anti-GT1a IgG antibodies were detected in both patients. When unusual psychiatric symptoms are observed, in addition to acute ophthalmoplegia and ataxia, neurologists should take into account the possibility of BBE. Brain MRI findings were normal in both patients and SPECT was performed on only patient 1. SPECT of patient 1 showed reversible hypoperfusion in the brainstem, bilateral thalami, and medial frontal lobe. Brain SPECT appears to be useful for detecting lesions of the brainstem as well as the basal ganglia or cerebrum in BBE.

Paradoxical cerebral embolism as the initial symptom in a patient with ovarian cancer.

This report concerns a 37-year-old patient with ovarian cancer and a paradoxical cerebral embolism as the initial symptom. She developed acute onset of left quadrantic hemianopia during coughing. Brain magnetic resonance imaging showed an acute multiple infarction, and a simultaneous acute pulmonary embolism was observed. Transesophageal echocardiography showed a patent foramen ovale, multidetector row computed tomography an ovarian tumor and infarction of the spleen, whereas multidetector row computed tomography venography showed right iliac vein compression by the ovarian tumor. The diagnosis was stage Ic ovarian cancer. Because blood stasis of the pelvic vein is a major risk factor for venous thrombosis, the presence of a patent foramen ovale should alert physicians to examine not only veins in the lower extremities but also the pelvic and intra-abdominal veins as a source paradoxical embolism.

[Successful use of methylprednisolone therapy in a case of non-herpetic acute encephalitis with antibodies against ionotropic glutamate receptor epsilon2 and delta2].

This report concerns a 32-year old man with non-herpetic acute limbic encephalitis. He was admitted to our hospital because of high fever and consciousness disturbance. Cranial MRI revealed abnormal signal intensities in the bilateral mesial temporal lobes. On the second hospitalization day, he developed status epilepticus, which necessitated general anesthesia. Following administration of intravenous (IV) methylprednisolone pulse therapy (1 g/day, 3 days), his consciousness disturbance began to improve. Treatment with high-dose IV methylprednisolone was continued for about 2 weeks, but on the 7th day, he showed severe anterograde amnesia and retrograde amnesia regarding the preceding 5 or 6 years. Subsequently, however, his amnesic disorders improved markedly, and on the 46th day, memory dysfunction had disappeared. Autoantibodies against the glutamate receptor subunits epsilon2 and delta2 were detected in both the CSF and serum, but these antibodies in the CSF became normal during the clinical course. The voltage-gated potassium channel antibody was negative. This case report indicates that high-dose IV methylprednisolone therapy may be an affective treatment for non-herpetic acute limbic encephalitis, possibly associated with autoimmune mechanisms.

A case of diabetic amyotrophy with severe atrophy and weakness of shoulder girdle muscles showing good response to intravenous immune globulin.

A 45-year-old man with insulin-dependent diabetic mellitus developed progressive asymmetrical weakness and atrophy of both shoulder girdle muscles within 1 year. In the last month, he also developed slight weakness of both thighs. Neuropathology of the sural nerve showed an axonal degeneration and perivascular inflammation and electromyography revealed neurogenic changes. Because of a diagnosis of suspected diabetic amyotrophy, intravenous immunoglobulin was administered. This treatment produced marked improvement. Physicians should take into account the possibility of diabetic amyotrophy in patients with diabetic mellitus showing primary involvement of shoulder girdle muscles marked by weakness and atrophy.

[A case of acute oropharyngeal palsy with nasal voice as main symptom].

We report a patient with acute oropharyngeal palsy following enteritis. A 19-year-old woman developed increasing nasal voice over a few days. Neurological examination on day 7 of her course showed paretic dysarthria and mild weakness of neck flexion and quadriceps femoris muscle (Medical Research Council grade, 4+). Her palatal movement was diminished, whereas both palatal and pharyngeal reflex was normal. She could swallow water, although she had a slight amount of liquid reflux to her nose on swallowing. High titers of serum anti-Campylobacter jejuni, anti-GQ1b and anti-GT1a IgG antibodies were detected. Her symptoms improved gradually without any treatment, and disappeared by 40 days from neurological onset. Nasal voice with slight swallowing impairment as initial symptom has been rarely reported, but can occur in acute oropharyngeal palsy. Therefore, neurologists should take into account the possibility of Guillain-Barré syndrome and the regional variants in patients who show nasal voice during the initial stage.

Bilateral iliopsoas hematomas complicating anticoagulant therapy.

An 85-year-old woman receiving anticoagulant therapy for transient ischemic attack suddenly developed bilateral femoral nerve palsy and severe pain in the bilateral groin and thighs. Her platelet count, prothrombin time and activated partial thromboplastin time were within the therapeutic range. Hematomas in the bilateral iliopsoas muscles were clearly detectable on CT scan. The right hematoma was larger than the left one and caused more severe femoral neuropathy, but improved gradually without surgical decompression. This case is reported here because bilateralism is exceptional, and iliopsoas hematoma should be suspected when a patient receiving anticoagulant therapy presents with pain in the groin or thigh.

Infectious endocarditis associated with subarachnoid hemorrhage, subdural hematoma and multiple brain abscesses.

Hemorrhagic stroke is a complication of infectious endocarditis (IE), and severe hemorrhage accompanies Staphylococcus aureus IE during early uncontrolled infection. However, subarachnoid hemorrhage (SAH) or subdural hematoma is rare. A case of S. aureus IE associated with SAH and subdural hematoma in the early stage is reported. A 54-year-old man with a history of mitral valve prolapse presented with fever. Two days after the onset, he fell into a confused state with convulsion and left hemiparesis. He became comatose and brain CT and MRI demonstrated SAH and subdural hematoma with severe right hemisphere swelling. Multiple brain abscesses were also observed. No septic aneurysm was detected by cerebral angiography.

[A patient with primary Sjögren's syndrome featuring polyneuropathy and oculomotor paralysis and associated with asymptomatic left middle cerebral artery stenosis].

We report a case of primary Sjögren's syndrome (primary SjS) with polyneuropathy and right oculomotor paralysis associated with middle cerebral artery stenosis. A 39-year-old woman developed progressive numbness and clumsiness of the limbs. Two months later, right third cranial palsy manifested itself and she was admitted to our hospital. A cranial MRA showed left middle cerebral artery stenosis confirmed by transcranial color doppler sonography. A nerve conduction study showed a decrease in the NCV and reduced CMAP, while sural nerve biopsy showed axonal degeneration and infiltration of inflammatory cells around the small blood vessel walls. The patient complained of dry mouth and a salivary gland biopsy revealed inflammatory changes, while salivary gland scintigraphy showed diminished secretion. These findings led to the diagnosis of Sjögren's syndrome. Reports of primary SjS with involvement of large cerebral arteries are rare. In our case, polyneuropathy and oculomotor paralysis were the manifest symptoms, but middle cerebral artery stenosis was also observed. This indicates that, even in the absence of CNS symptoms, cerebral artery involvement may be present in primary SjS.

Unequal crossing-over in unique PABP2 mutations in Japanese patients: a possible cause of oculopharyngeal muscular dystrophy.

BACKGROUND: Oculopharyngeal muscular dystrophy (OPMD) is an adult-onset autosomal dominant muscle disease with a worldwide distribution. Recent findings reveal the genetic basis of this disease to be mutations in the polyA binding-protein 2 (PABP2) gene that involve short expansions of the GCG trinucleotide repeat encoding a polyalanine tract. The underlying mechanism causing the triplet-expansion mutation in PABP2 remains to be elucidated, although the DNA slippage model is thought to be a plausible explanation of that. METHODS AND RESULTS: We analyzed PABP2 using polymerase chain reaction analysis and DNA sequencing in Japanese patients with pathologically confirmed OPMD, and found mutated (GCG)(6)GCA(GCG)(3)(GCA)(3)GCG and (GCG)(6)(GCA)(3)(GCG)(2)(GCA)(3)GCG alleles instead of the normal (GCG)(6)(GCA)(3)GCG allele. These mutated alleles could be explained by the insertions or duplications of (GCG)(3)GCA and (GCG)(2)(GCA)(3), respectively, but not by the simple expansion of GCG repeats. The clinical features of our patients were compatible with those of other Japanese patients carrying PABP2 that encodes a polyalanine tract of the same length, but were not compatible with those of Italian patients. CONCLUSIONS: The mutated alleles identified in our Japanese patients with OPMD were most likely due to duplications of (GCG)(3)GCA and (GCG)(2)(GCA)(3) but not simple expansions of the GCG repeats. Therefore, unequal crossing-over of 2 PABP2 alleles, rather than DNA slippage, is probably the causative mechanism of OPMD mutations. All mutations that have been reported in patients with OPMD so far can be explained with the mechanism of unequal crossing-over. On the other hand, comparison of the clinical features of our patients with those of other patients in previous reports suggests that specific clinical features cannot be attributed to the length of the polyalanine tract per se.