Distribution of Deep Gray Matter Lesions on Magnetic Resonance Imaging in Lymphomatosis Cerebri.

We herein report the distribution of gray matter lesions on magnetic resonance imaging (MRI) in two patients with lymphomatosis cerebri (LC). In our patients, the fluid-attenuated inversion recovery sequence of brain MRI demonstrated a bilateral and diffuse high signal intensity, not only in the white matter but also in the thalamus, globus pallidus, putamen, and hippocampus. Among the deep gray matter, the caudate head and putamen (striatum) were relatively spared when compared with the globus pallidus, thalamus, and hippocampus. Interestingly, we found seven previous reports of similar MRI findings, with relative sparing of the striatum, in patients with LC. This finding may be characteristic of LC and help facilitate its diagnosis. Further investigations of a larger number of LC patients are necessary to confirm these findings.

Paradoxical Cerebral Embolism as Initial Manifestation of Chronic Thromboembolic Pulmonary Hypertension: A Case Report.

Chronic thromboembolic pulmonary hypertension (CTEPH) is characterized by chronic thrombi in the pulmonary arteries, causing pulmonary hypertension and right heart failure. Early and accurate diagnosis are essential for successful treatment but are often difficult because clinical signs and symptoms can be nonspecific and risk factors, such as history of venous thromboembolism, may not always be present. Here, we report a case involving a 76-year-old woman who demonstrated paradoxical cerebral embolism as the initial manifestation of CTEPH. She developed right hemiplegia without dyspnea or edema. Brain magnetic resonance imaging revealed multiple fresh infarctions, while transesophageal echocardiography revealed a patent foramen ovale. Based on these findings, she was diagnosed as having paradoxical cerebral embolism. During the search for the embolic source, right heart catheterization showed significant pulmonary hypertension and pulmonary angiography revealed chronic thrombi in the peripheral pulmonary arteries, consistent with a diagnosis of CTEPH. To our knowledge, this is the first case of CTEPH to be diagnosed with the onset of paradoxical cerebral embolism. Because CTEPH is the only potentially curable form of pulmonary hypertension, clinicians should consider paradoxical cerebral embolism as a possible initial manifestation of CTEPH.

Retrobulbar optic neuropathy associated with sphenoid sinus mucormycosis.

Because fungi usually spread from the paranasal sinuses to the orbital apex in invasive fungal sinusitis (IFS), IFS often presents as an orbital apex syndrome (OAS) characterized by dysfunction of cranial nerves II, III, IV, V1, and VI. We report a case of sphenoid sinus mucormycosis that presented as isolated retrobulbar optic neuropathy. A 94-year-old woman presented with acute blindness in the right eye. Examination revealed the absence of light perception and pupillary reflex in the right eye. Head MRI showed a mass in the right sphenoid sinus, which was contiguous with the right optic nerve. She underwent endoscopic surgery, and a histopathological diagnosis of mucormycosis was established. Treatment with intravenous liposomal amphotericin B reduced the size of the mass. She has survived for more than 1 year without recurrence. Clinicians should consider that IFS can present as isolated retrobulbar optic neuropathy.

Acute pancreatitis is a very rare comorbidity of acute ischemic stroke.

Background: Although acute pancreatitis is listed among the exclusion criteria for the administration of recombinant tissue plasminogen activator according to the Japanese Guideline for the Management of Stroke, the co-occurrence of acute pancreatitis and acute ischemic stroke has not been investigated. The present study aimed to assess the incidence rate of acute pancreatitis in patients with acute ischemic stroke. Methods: This study consecutively enrolled all patients with ischemic stroke admitted to the Department of Neurology, JA Toride Medical Center between April 2014 and March 2016. Diagnosis of acute pancreatitis was made according to the revised Atlanta Classification of Acute Pancreatitis. We retrospectively analyzed serum amylase activity and the frequency of acute pancreatitis as a comorbidity of ischemic stroke. Results: A total of 411 ischemic stroke patients were included. Serum amylase activity was measured for 364 patients, 27 of whom presented with amylase activity exceeding the upper limit of normal. In two patients with serum amylase activity greater than three times-fold the upper limit of normal, computed tomography or transabdominal ultrasonography showed no characteristic findings of acute pancreatitis. No patient in the cohort met the diagnostic criteria for acute pancreatitis. Conclusions: Acute pancreatitis is a very rare comorbidity of acute ischemic stroke.

[Dropped head syndrome as first manifestation of primary hyperparathyroid myopathy].

75 years old woman presented with 6-month history of progressive dropped head syndrome. Neurological examination revealed moderate weakness of flexor and extensor of neck and mild weakness of proximal appendicular muscles with normal deep tendon reflexes. The needle electromyography showed short duration and low amplitude motor unit potential. No fibrillation potentials or positive sharp waves were seen. Biopsy of deltoid muscle was normal. Laboratory studies showed elevated levels of serum calcium (11.8 mg/dl, upper limit of normal 10.1) and intact parathyroid hormone (104 pg/ml, upper limit of normal 65), and decreased level of serum phosphorus (2.3 mg/dl, lower limit of normal 2.7). Ultrasonography and enhanced computed tomography revealed a parathyroid tumor. The tumor was removed surgically. Pathological examination proved tumor to be parathyroid adenoma. Dropped head and weakness of muscles were dramatically improved within a week after the operation. Although hyperparathyroidism is a rare cause of dropped head syndrome, neurologists must recognize hyperparathyroidism as a treatable cause of dropped head syndrome.

Gene dosage effect in spinocerebellar ataxia type 6 homozygotes: A clinical and neuropathological study.

Spinocerebellar ataxia type 6 (SCA6) is an autosomal dominant neurodegenerative disorder. However, it remains unclear whether SCA6 shows a gene dosage effect, defined by earlier age-of-onset in homozygotes than heterozygotes. Herein, we retrospectively analyzed four homozygous SCA6 subjects from our single institution cohort of 120 SCA6 subjects. We also performed a neuropathological investigation into an SCA6 individual with compound heterozygous expansions. In the 116 heterozygotes, there was an inverse correlation of age-of-onset with the number of CAG repeats in the expanded allele, and with the total number of CAG repeats, in both normal and expanded alleles. The age-of-onset in the four homozygotes was within the 95% confidence interval of the age-of-onset versus the repeat-lengths correlations determined in the 116 heterozygotes. Nevertheless, all homozygotes had earlier onset than their parents, and showed rapid disease progression. Neuropathology revealed neuronal loss, as well as α1A-calcium channel protein aggregates in Purkinje cells, a few α1A-calcium channel protein aggregates in the neocortex and basal ganglia, and neuronal loss in Clarke's column and the globus pallidus not seen in heterozygotes. These data suggest a mild clinical and neuropathological gene dosage effect in SCA6 subjects.

Relocation of p25α/tubulin polymerization promoting protein from the nucleus to the perinuclear cytoplasm in the oligodendroglia of sporadic and COQ2 mutant multiple system atrophy.

p25α/tubulin polymerization promoting protein (TPPP) is an oligodendroglial protein that plays crucial roles including myelination, and the stabilization of microtubules. In multiple system atrophy (MSA), TPPP is suggested to relocate from the myelin sheath to the oligodendroglial cell body, before the formation of glial cytoplasmic inclusions (GCIs), the pathologic hallmark of MSA. However, much is left unknown about the re-distribution of TPPP in MSA. We generated new antibodies against the N- and C-terminus of TPPP, and analyzed control and MSA brains, including the brain of a familial MSA patient carrying homozygous mutations in the coenzyme Q2 gene (COQ2). In control brain tissues, TPPP was localized not only in the cytoplasmic component of the oligodendroglia including perinuclear cytoplasm and peripheral processes in the white matter, but also in the nucleus of a fraction (62.4%) of oligodendroglial cells. Immunoelectron microscopic analysis showed TPPP in the nucleus and mitochondrial membrane of normal oligodendroglia, while western blot also supported its nuclear and mitochondrial existence. In MSA, the prevalence of nuclear TPPP was 48.6% in the oligodendroglia lacking GCIs, whereas it was further decreased to 19.6% in the oligodendroglia with phosphorylated α-synuclein (pα-syn)-positive GCIs, both showing a significant decrease compared to controls (62.4%). In contrast, TPPP accumulated in the perinuclear cytoplasm where mitochondrial membrane (TOM20 and cytochrome C) and fission (DRP1) proteins were often immunoreactive. We conclude that in MSA-oligodendroglia, TPPP is reduced, not only in the peripheral cytoplasm, but also in the nucleus and relocated to the perinuclear cytoplasm.

[Optic nerve swelling and gadolinium contrast enhancement on magnetic resonance imaging in the subacute stage of Leber's hereditary optic neuropathy: a case report].

We report the case of a 50-year-old man with subacute onset of bilateral visual field loss and visual acuity loss. His visual acuity was 0.07 OD/0.09 OS and Goldmann perimetry showed central scotomas. The optic fundi were normal bilaterally. Magnetic resonance imaging (MRI) showed hyperintensity in the right optic nerve on T(2) weighted imaging and swelling of the optic chiasm with slight enhancement of the bilateral optic nerves and the optic chiasm on gadolinium-enhanced imaging. Since sensory disturbance in the left hand and leg was noted in addition to the visual problem, multiple sclerosis (MS) was suspected initially. The patient was treated with intravenous methylprednisolone (1,000 mg/day), plasma exchange therapy, and immunosuppressant therapy. However, his visual disturbance did not improve. He had a history of deafness and family history of visual disturbance, because of which we performed an analysis of mitochondrial DNA. G11778A point mutation was found, and a diagnosis of Leber's hereditary optic neuropathy (LHON) was made. Although gadolinium contrast enhancement and swelling of the optic nerve are rare, this case shows that these findings are not in conflict with LHON. The present case also suggests that mitochondrial dysfunction may trigger the onset of MS-like extraocular symptoms in patients with LHON.

18F-FDG PET successfully detects spinal cord sarcoidosis.

Though there has been an array of methods to evaluate the extent of sarcoidosis, it is generally difficult to detect central nervous system involvement. Recently it has become accepted that 18F-FDG PET is more sensitive than gallium scintigraphy in finding sarcoid lesions, however its usefulness and limitations for detecting sarcoidosis in the central nervous system, especially in the spinal cord, has rarely been investigated. Two patients with pathologically confirmed sarcoidosis manifested spinal symptoms. We conducted 18F-FDG PET along with conventional imagings before and after treatment. Abnormal FDG uptakes which could not be detected by gallium scintigraphy were shown in the spinal cords in both patients. These abnormal uptakes were diminished in accordance with clinical improvement after treatment. Our findings suggest that 18F-FDG PET is effective in detecting and tracking the activity of spinal sarcoidosis.