Rapidly progressive psychotic symptoms triggered by infection in a patient with methylenetetrahydrofolate reductase deficiency: a case report.

BACKGROUND: Methylenetetrahydrofolate reductase (MTHFR) deficiency is a rare inborn error of metabolism inherited in autosomal recessive pattern and is associated with a wide spectrum of neurological abnormalities. CASE PRESENTATION: We herein describe a 15-year-old boy with MTHFR deficiency who presented with a slowly progressive decline of school performance and a spastic gait. Rapidly deteriorating psychosis and repetitive seizures triggered by a febrile infection prompted neurological investigation. He had significantly elevated total plasma homocysteine and urinary homocystine levels, as well as a decreased plasma methionine level. Brain magnetic resonance imaging (MRI) revealed leukoencephalopathy. DNA gene sequencing showed c.446_447 del GC ins TT and c.137G > A, and c.665C > T heterozygous mutations in the MTHFR gene of the patient. Oral administration of betaine drastically improved his clinical symptoms within a few months. After 8 months of treatment, his total plasma homocysteine level moderately decreased; and the plasma methionine concentration became normalized. Furthermore, the white matter lesions on MRI had disappeared. CONCLUSION: This patient demonstrates the possibility that MTHFR deficiency should be considered in mentally retarded adolescents who display an abnormally elevated plasma level of homocysteine in association with progressive neurological dysfunction and leukoencephalopathy. Febrile infections may be an aggravating factor in patients with MTHFR deficiency.

Weight loss in the early stage of progressive supranuclear palsy.

OBJECTIVES: To clarify whether weight change in patients with Parkinson's disease (PD) or progressive supranuclear palsy (PSP) is caused by the disease itself or secondarily by other factors. MATERIALS AND METHODS: We conducted a retrospective analysis of 51 patients with PD and 14 patients with PSP, especially during the early stage of their diseases. All patients were independent in terms of their activities of daily living and did not have any feeding difficulty. RESULTS: The body mass index measured within 3 years after the disease onset did not show a significant difference between the two diseases. However, the subsequent weight was stable in patients with PD and significantly decreased in patients with PSP. CONCLUSIONS: Weight loss begins in the early stage of PSP, whereas dopaminergic treatment may contribute to keep weight in the early stage of PD through reduction of energy expenditure and/or improvement in appetite.

A case of progressive multifocal leukoencephalopathy with chronic renal failure, whose JC virus in cerebrospinal fluid disappeared after mefloquine-mirtazapine dual therapy.

An 83-year-old man with chronic renal failure was referred to our hospital because of subacute progressive right hemiparesis. A brain MRI showed high-intensity lesions in bilateral middle cerebellar peduncles and white matter of the left frontal lobe on T2-weighted images. The lesions increased gradually, so we suspected a brain tumor because 1H-MRS images showed elevated Cho and decreased NAA, and also pathologic findings of the brain biopsy suggested glioblastoma. However, JC virus (JCV) in cerebrospinal fluid was revealed highly positive by PCR. So we reconsidered pathologically and finally found bizarre astrocytes which were infected with JCV in immunohistochemical studies and we diagnosed progressive multifocal leukoencephalopathy at last. Then we medicated with mefloquine and mirtazapine, and the JCV in cerebrospinal fluid disappeared, without new MRI lesions. This is a rare case in respect of the background of the patient and the clinical course.

Early-onset Parkinson's Disease Associated with Chromosome 22q11.2 Deletion Syndrome.

We herein report the case of a 43-year-old man with a 4-year history of resting tremor and akinesia. His resting tremor and rigidity were more prominent on the left side. He also presented retropulsion. His symptoms responded to the administration of levodopa. The patient also had a cleft lip and palate, cavum vergae, and hypoparathyroidism. A chromosome analysis disclosed a hemizygous deletion in 22q11.2, and he was diagnosed with early-onset Parkinson's disease associated with 22q11.2 deletion syndrome. However, the patient lacked autonomic nerve dysfunction, and his cardiac uptake of (123)I-metaiodobenzylguanidine was normal, indicating an underlying pathological mechanism that differed to that of sporadic Parkinson's disease.

Slowly progressive Lemierre's syndrome with orbital pain and exophthalmos.

Lemierre's syndrome is an oropharyngeal bacterial infection characterized by rapidly progressive septic thrombophlebitis of the internal jugular vein. A lack of appropriate antibiotic therapy can be life-threatening. We describe the case of a 39-year-old man with Lemierre's syndrome who presented with long-lasting orbital pain and acute exophthalmos 6 weeks after initial infection. This report is to help clinicians consider the diagnosis of Lemierre's syndrome when encountering a patient with long-lasting orbital pain and acute exophthalmos. Neck ultrasonography is useful for detecting thrombophlebitis of the internal jugular vein in Lemierre's syndrome patients.

[Successful treatment of neuromyelitis optica spectrum disorder by early initiation of plasma exchange].

A 39-year-old woman initially developed vomiting and intractable hiccup, followed by progressive dysphagia, dysarthria and hypoglossal nerve palsy. She was admitted to our department on the 30th day of illness. MRI-FLAIR images of the brain revealed a hyperintense lesion in the dorsal medulla. A diagnosis of neuromyelitis optica spectrum disorder (NMOSD) was entertained according to the clinical course and the MRI images. The dysphagia was intractable to methylprednisolone pulse therapy, and so a course of plasma exchange therapy was initiated on the 32nd day of illness. After the third plasma exchange, the symptoms began to improve. Thereafter the patient's serum on admission was reported as positive for anti-aquaporin-4 antibody. Considering the irreversible nature of NMOSD pathology, early initiation of plasma exchange therapy is recommended to minimize the lesion in the case of steroid-refractory NMOSD patients.

An autopsy case of sporadic amyotrophic lateral sclerosis associated with the I113T SOD1 mutation.

A 64-year-old man noticed weakness in his arms and dyspnea upon exertion. Four months later he was admitted to our hospital, where muscle atrophy and hyperactive deep tendon reflexes in the arms were observed upon examination. A needle electromyograph study revealed acute and chronic denervation in the extremities, and he was diagnosed as having amyotrophic lateral sclerosis (ALS). Seven months after onset of the disease, he died of respiratory failure. Neuropathologically, neuronal cell loss was observed in the motor cortex, hypoglossal nuclei, cervical and lumbar anterior horns and Clarke's nuclei. Some of the remaining neurons contained neurofilamentous conglomerate inclusions (CIs). A small number of Lewy body-like hyaline inclusions (LBHIs) were also observed. No the Bunina bodies, skein-like inclusions or basophilic inclusions were detectable. Tract degeneration was moderate in the dorsal and ventral spinocerebellar tracts, mild in the pyramidal tract, but not discerned in the posterior column. Immunohistochemical examinations revealed that the CIs were strongly positive for phosphorylated neurofilament and moderately positive for ubiquitin and Cu/Zn superoxide dismutase 1 (SOD1). Moreover, a number of phosphorylated tau protein-positive globose neurofibrillary tangles (NFTs) and threads were observed in the periaqueductal gray matter, oculomotor nuclei and trochlear nuclei. Although the family history was negative for neuromuscular diseases, the neuropathological findings indicated features of familial ALS with a SOD1 mutation. In fact, DNA analysis of frozen-brain tissue revealed the presence of the I113T SOD1 mutation. This case represents the first one of this mutation in a patient who showed CIs as well as LBHIs in the motor neurons at the same time, in addition to the NFTs in the mesencephalic tegmentum.

[A case of cerebellar syndrome associated with HIV infection].

A 36-year-old man was hospitalized because of subacutely progressive gait disturbance. Neurological examination disclosed severe ataxia of gait and trunk and moderate ataxia of the four limbs, without signs of cognitive impairment. There were no manifestations of systemic infections. Brain MRI showed mild atrophy of the cerebellar vermis and hemispheres. Extensive laboratory search failed to disclose the cause of subacute ataxia. Cerebellar ataxia progressed, leading to the patient becoming wheelchair-bound two months after admission, when PCR analysis of the cerebrospinal fluid was positive for Epstein-Barr, JC, and hepatitis B viruses. In addition, the quantity of serum HIV1-RNA was 2.9 x 10(4) copies, the absolute count of CD4+ lymphocyte was 28/mm3, and the CD4/CD8 ratio was 0.04, despite clear denials by both the patient and his wife regarding any apparent infectious opportunities. Accordingly thereafter, highly active antiretroviral therapy was initiated. Several weeks after the initiation of therapy, ataxia stabilized with disappearance of serum HIV and cerebrospinal fluid JCV viral load. He returned to his occupation 20 months after disease onset without progression of ataxia or development of other neurological dysfunctions including dementia. We could not establish the exact pathogenesis of ataxia in this patient It could have been primary cerebellar degeneration caused by HIV, or the other viruses detected (EBV, JCV) or autoimmune mechanisms caused by these viruses. However, HIV infection should be considered as an etiology in clinical setting of subacute ataxia, particularly in a young or immunocompromised patient.

[Bilateral gustatory disturbance associated with left putaminal hemorrhage].

We reported a 39-year-old, left-handed man with sudden onset hypogeusia. Taste threshold examined by a filter-paper disc method was elevated remarkably on both sides of the tongue. Additionally, the patient showed mild right central facial nerve palsy and mild weakness in the right upper limb. Brain CT showed left putaminal hemorrhage. Brain MRI demonstrated a hemorrhage in the left putamen and edema affecting the insular cortex. In this case, the gustatory information from both sides of the tongue, regardless of whether the nerves cross in a brainstem, is suggested to project to the left insular cortex before ascending to the higher order taste and language areas.