Rasmussen syndrome (RS) and non-herpetic acute limbic encephalitis (NHALE) have pathophysiological background related with autoimmunity to glutamate receptors (GluRs) after infections. RS and NHALE were reviewed, depending mainly on our recent studies. RS is the prototype of autoimmune-mediated epilepsy. In patients with RS, several kinds of autoantibodies against neuronal molecules, for example, GluR3, GluRε2 (NMDA-R2B), etc., are reported. These autoantibodies are not specific for RS. About autoantibodies against GluR3, significance and stimulating effects to GluR3 are controversial. Autoantibodies against GluRε2 were detected in all patients within six months from epilepsy onset, and in some patients at chronic stage. These data suggest that autoantibodies against GluRε2 may be involved in the pathological mechanisms in the early stage, but we could not confirm the effect of the autoantibodies from RS patients on excitatory postsynaptic NMDA current using patch clump methods. However, anti-double-stranded DNA antibodies in patients with SLE are reported to cross-react with n-terminal of GluRε2, and cause neuronal apoptosis in rat hippocampus, ensuing memory impairment, and emotional behavior impairment in mice. Therefore, autoantibodies against GluRε2 may contribute to the cognitive and behavioral changes in RS. Concerning about cellular immunity in RS, lymphocytes stimulating tests revealed peripheral lymphocytes sensitized by antigens containing GluRε2. Cytotoxic T cells (CTLs) excreting Granzyme B were reported in resected brain tissue, and we confirmed the elevated levels of Granzyme B, not in sera, but in CSF. These data suggest that CTLs activated by infection invade into CNS, and recognize neural antigens, and excrete Granzyme B. The incidence of NHALE is 4.1/1 million/year in Japanese adults. Our study in 91 adult patients with NHALE revealed the following characteristics. Mean onset age was 35.2±16.9 years old, and preceding infections existed in 68.7% of patients, and predominant symptoms at the onset were psychiatric symptoms (33.3%) and convulsions (25.0%). CSF showed slightly elevated cell counts (55.5±139.9), protein levels (48.1±36.0mg/dl), and IgG levels (4.5±3.9mg/dl). MRI lesions with high intensity were found in 40.8% (DWI) and 54.2% (FLAIR) of patients in various stages after onsets. Autoantibodies against GluRε2 in sera were detected in approximately 60% of NHALE patients from acute to chronic stages, and the autoantibodies in CSF were detected in 51.8% (acute stage), 41.4% (recovery stage), 28.6% (chronic stage) of patients and included epitopes to n-terminal of GluRε2 (NT1). These data suggest that autoantibodies against GluRε2 produced in sera after infection infiltrate into CNS through damaged BBB in acute stages, and affect n-terminal of GluRε2. In chronic stage, recovery of function of BBB reduces levels of the autoantibodies in CSF. Because BBB in hippocampi and amygdala are vulnerable, autoantibodies against GluRε2 including epitopes to n-terminal may contribute to the limbic symptoms around onset. Among several autoantibodies related with NHALE, autoantibodies against GluRε2 were found in patients around 15-34 years old, autoantibodies against VGKC were around 50.4 years old, autoantibodies against NAE were around 59 years old, autoantibodies against Hu were around 61.5 years old. These data suggest that autoantibodies related with NHALE have age-dependent heterogeneity.
Clinical features and courses of 5 cases with HIV encephalopathy were reported. The subjects were among the patients registered as HIV patients at the Nagoya Medical Center, between 1996 and 2005. There were 458 patients with HIV infection including 127 cases of AIDS. All patients suffered from severe immunological deficiency when HIV encephalopathy developed. Other opportunistic infections had also occurred in three patients. HIV encephalopathy was one of the presenting manifestations of HIV infection in four patients, and no patients had received antiretroviral therapy. HAART improved motor disturbance and their ADL became independent except for one case. Improvements in neuropsychological examination scores were noted in all cases. Recovery from psychiatric symptoms, however, was incomplete. Four patients could not work, and 3 needed psychological treatment due to behavioral abnormalities. HIV encephalopathy is not a lethal disease but the functional prognosis was very poor. New therapy is needed for HIV encephalopathy.
We reported a 51-year-old woman with Gerstmann-Sträussler-Scheinker syndrome (GSS P102L) manifesting characteristic MRI findings. At the age of 45, She developed gait disturbance with muscle atrophy in the lower limbs and positive plantar flexor sign. Subsequently, sensory disturbance such as refractory pain in the lower limbs and ataxic gait were developed at the age of 49. Following these clinical symptoms, she finally demonstrated rapid progressive cognitive dysfunction. Just after presenting cognitive dysfunction, cranial MRI was performed. Cranial MRI with diffusion-weighted imaging and FLAIR imaging demonstrated abnormal high intensity lesions in the bilateral pulvinar, caudate nuclei and cerebral cortex. The degree of high signal at the pulvinar was less than those of the cortex and caudate nuclei. A proline-for-leucine substitution at codon 102 of the prion protein gene was demonstrated. These results allowed the diagnosis of GSS (P102L). This is a rare case of GSS (P102L) presenting with high intensity lesions in the bilateral pulvinar on MRI.
We report a case of syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) associated with limbic encephalitis. A 79-year-old woman was admitted with a complaint of fever, disturbance of consciousness and generalized seizure. Her conscious level was E1V2M4 by Glasgow coma scale. Physical examination showed generalized seizure, neck stiffness, hyperreflexia and flaccid paralysis in her all extremities, and pathological reflexes. Blood analysis revealed hyponatremia, decrease of plasma osmolarity, spared secretion of urine sodium and increase of ADH, leading to the diagnosis of SIADH. Cerebrosponal fluid examination showed mild pleocytosis, elevated protein, and normal glucose level. Although herpes simplex virus (HSV) DNA was not detected by the polymerase chain reaction method, titers of anti-HSV IgG antibody elevated chronologically. Brain MRI revealed abnormal T2 and FLAIR high intensities in the cingulate gyrus and hippocampus bilaterally. An EEG revealed periodic synchronous discharges predominantly in the frontal areas. Based on the clinical course, laboratory data, MRI and EEG findings, we diagnosed as SIADH associated with acute limbic encephalitis caused by HSV infection. After the fluid restriction and sodium supply, plasma sodium was normalized. Administration of acyclovir and steroid was not so effective, however her condition improved gradually. Several cases of SIADH associated with limbic encephalitis have been reported; however, the pathophysiology is to be clarified. We thought that in the presented case, SIADH was caused by disturbance of the hormonal control at the hypothalamus on the pituitary gland due to the spreading of inflammation from limbic system to these areas.
We report a 63-year-old man with rheumatoid meningitis. At 47-years-old, he developed rheumatoid vasculitis causing arthralgia and skin ulcer. Although the patient had been treated with prednisolone and cyclosporine A, headache and recurrent focal seizures of the right upper limb and generalized seizures developed. Brain magnetic resonance imaging showed high signal intensity lesions on FLAIR MRI and associated abnormal enhancement of the leptomeninges. Part of the lesions also showed patchy high signal intensity on diffusion-weighted imaging (DWI). This features may be useful for differentiating rheumatoid meningitis from subdural empyema, because the extent of the lesions on DWI matches the lesion on FLAIR imaging in patients with subdural empyema. Cerebrospinal fluid analysis revealed monocytic pleocytosis and negative findings for infection or malignancy. After intravenous administration of methylprednisolone (1,000mg/day for 3 days), the patient showed improvements in headache, cerebrospinal fluid findings and abnormal hyperintensity on DWI. Rheumatoid meningitis is an extremely rare neurological manifestation, but careful attention should be paid even in the inactive stage of rheumatoid arthritis. This disease tends to present with unilateral supratentorial lesions. In this case, serial diffusion-weighted and FLAIR MRI was useful for following the leptomeningeal lesions.
A 32-year-old man who had experienced fever and a pulsating headache of the right occipital region for a month and a transient left hemianopia and numbness in the left arm two weeks prior to presentation was admitted to our hospital because of a seizure. Fluid-attenuated inversion recovery and diffusion-weighted magnetic resonance imaging (MRI) showed high-intensity signals, without reduction of apparent diffusion coefficient value, in the right temporo-occipital cortices. Proton MR spectroscopy (1H-MRS) indicated a decrease in N-acetyl-aspartate, and single-photon emission CT (SPECT) showed hyperperfusion in the right temporo-occipital territory. An examination of the cerebrospinal fluid showed an elevation of mononuclear cells and the presence of anti-glutamate ε2 receptor antibodies. All abnormalities shown by these imaging techniques were normalized in the clinical course. This report suggests that MRI, 1H-MRS and SPECT studies were useful in understanding the pathogenesis of encephalitis associated with glutamate receptor antibodies.
A 67-year-old man was admitted to our hospital in May 2006 because of gait disturbance, delirium and myoclonus along with dermatitis and diarrhea. Those symptoms became worse in 3 months. He had undergone a gastrectomy, including a fundectomy and jejunal pouch interposition, for early gastric cancer at the age of 65 years. He had no habit of drinking alcohol or unbalanced diet. The triad of typical dermatitis, delirium, and diarrhea led to a diagnosis of pellagra, and all the symptoms disappeared after intravenous administration of nicotinate and vitamins. With a gastrectomy, fundectomy performed with jejunal pouch interposition has been regarded as a superior method for postoperative nutrition, but may cause vitamin deficiency. Thus, vitamin deficiency must be considered as a potential cause in neurologic patients who underwent surgical treatment for disorders of digestive tract, regardless of the procedure utilized.
A 59-year-old man had have dysuria and left thigh pain for 2 months. He also experienced transient weakness of both legs twice, which recovered within a few hours. One month ago, he had bowel disturbance. Lumbar MRI showed a swelling of the conus medullaris. Enlarged and tortuous vessels behind the spinal cord on lumbar MRA and CT myelography was demonstrated. Though angiogram through intercostal and lumbar arteries revealed no abnormal findings, CT angiography with multidetector row helical CT (MDCT) showed abnormal vessel in intradural space at sacral level. Angiogram through left internal iliac artery revealed abnormal vessel fed by branches of the lateral sacral artery at the early arterial phase. Thus, diagnosis of dural arteriovenous fistula (DAVF) at the left S1 level was confirmed. It was indicated that CT angiography with MDCT was useful in detecting spinal DAVF especially at sacral level.
A 34-year-old man with astrocytoma in the left parietal lobe had symptomatic partial epilepsy, and he presented transient episodes of acalculia, agraphia and finger agnosia. Occasionally he had difficulty in finding appropriate letters when making an e-mail, and difficulty in writing and calculation. Neurological examinations revealed ictal symptoms of Gerstmann's syndrome without right to left disorientation. No other higher cortical dysfunction or neurological deficits were noted. Scalp EEGs showed frequent, regional ictal discharges in the left parietal area lasting for 60-240 seconds. These clinico-electrographical observations strongly support that epileptic seizures produced a loss of cortical higher function manifesting Gerstmann's syndrome.