[Cerebral cortical encephalitis with anti-myelin oligodendrocyte glycoprotein (MOG) antibody].

A 27-year-old man developed acute encephalitis with headache, fever, seizures, and aphasia. Analysis of cerebrospinal fluid showed elevated levels of cell counts and protein. A brain MRI demonstrated increased FLAIR signals in the left cerebral cortex with cortical swelling. An MRA also showed mild vasodilatation of the left middle cerebral artery branches. After admission, severe psychomotor excitement developed. Immunotherapy with intravenous high-dose steroid and subsequent oral steroid was successful, and the patient returned to premorbid working position. Repeated MRI study showed complete resolution. Serum anti-myelin oligodendrocyte glycoprotein (MOG) antibody was positive, while anti-aquaporin-4 antibody, anti-N-methyl-D-aspartate (NMDA) receptor antibody, and other autoimmune antibodies were all negative. There were no relapses at final follow-up of 8 months after onset. Cerebral cortical encephalitis with unknown etiology can occur associated with anti-MOG antibody, and anti-MOG antibody may play certain role in the pathogenesis.

Anti-NMDA-Receptor Encephalitis: From Bench to Clinic.

NMDAR encephalitis is a common cause of autoimmune encephalitis, predominantly affecting young adults. Current data supports the idea that autoantibodies targeting NMDARs are responsible for disease pathogenesis. While these autoantibodies occur in the setting of underlying malignancy in approximately half of all patients, initiating factors for the autoimmune response in the remainder of patients are unclear. While there is increasing evidence supporting viral triggers such as herpes simplex encephalitis, this association and the mechanism of action have not yet been fully described. Although the majority of patients achieve good outcomes, those without an underlying tumor consistently show worse outcomes, prolonged recovery, and more frequent relapses. The cloning of patient-specific autoantibodies from affected individuals has raised important questions as to disease pathophysiology and clinical heterogeneity. Further advances in our understanding of this disease and underlying triggers are necessary to develop treatments which improve outcomes in patients presenting in the absence of tumors.

Bi-insular cortical involvement in anti-NMDA-receptor encephalitis - a case report.

BACKGROUND: Anti-NMDA-receptor encephalitis is an immune-mediated inflammatory disorder of the central nervous system. Brain MRI is unremarkable in at least 50% of patients and highly variable in the remaining patients with signal abnormalities in different brain regions. Only scarce reports exist on other imaging modalities. CASE PRESENTATION: A 31-year-old woman sub-acutely developed psychosis, behavioural changes, amnesia, alternating states of agitation and mutism, fever and epileptic seizures. Clinically suspected diagnosis of anti-NMDA-receptor encephalitis was confirmed by the detection of anti-NMDA receptor antibodies in CSF and serum. During the acute phase, brain MRI abnormalities were found in both insular cortices and hippocampi, whereas F(18)-FDG-PET showed hypermetabolism bilaterally in insular and prefrontal cortex. After resection of the underlying ovarian teratoma and with multimodal immunotherapy the patient substantially improved reaching a modified Rankin Scale score of 2 after 3 months. At follow-up, both hippocampi were still affected on MRI, whereas insular cortex appeared normal; however, both regions showed prominent glucose hypometabolism. CONCLUSIONS: Here, we report bi-insular cortical abnormalities on MRI and F(18)-FDG-PET in a patient with anti-NMDA-receptor encephalitis during the acute phase and after clinical improvement.

Primary Sjögren's syndrome is associated with significant cognitive dysfunction.

AIM: Cognitive dysfunction is a neurologic manifestation in primary Sjögren syndrome (PSS). On the other hand, several antibodies are related to cognitive dysfunction. The aim of this study is to assess the cognitive dysfunction of PSS patients via detailed neurologic tests. Moreover, its associations with antibodies were also evaluated. METHOD: Twenty-eight female patients with PSS and 17 healthy controls comprised the study groups. Short-term memory, long-term memory, verbal learning, visual memory, visual spatial perception, attention, verbal frequency function, executive functions and information processing speed were evaluated with neurologic tests in both of the study groups. Furthermore, anti-N-methyl-D-aspartate (NMDA) type anti-glutamate-receptor antibody, anti-ribosomal-p and antiganglioside antibodies were assessed in the study groups. RESULTS: The attention, data processing speed, verbal learning, short-term verbal memory and visuo-spatial perception performances were lower in the patients with PSS when compared to the healthy controls. The difference reached statistical significance in Paced Auditory Serial Addition Test (P < 0.01), Serial Digit Learning Test (P < 0.01), clock drawing (P = 0.03), Auditory Verbal Learning Test immediate verbal memory (P = 0.01) and Benton Judgement of Line Orientation Test (P = 0.03). Even if antiganglioside antibodies were more likely to be present in the PSS group when compared to the healthy controls, no relationship was found between its positivity and cognitive dysfunction. CONCLUSION: Results of this study suggest that cognitive dysfunction is quite prevalent in PSS patients without being associated with studied antibodies.

Effects of Anti-NMDA Antibodies on Functional Recovery and Synaptic Rearrangement Following Hemicerebellectomy.

The compensation that follows cerebellar lesions is based on synaptic modifications in many cortical and subcortical regions, although its cellular mechanisms are still unclear. Changes in glutamatergic receptor expression may represent the synaptic basis of the compensated state. We analyzed in rats the involvement of glutamatergic system of the cerebello-frontal network in the compensation following a right hemicerebellectomy. We evaluated motor performances, spatial competencies and molecular correlates in compensated hemicerebellectomized rats which in the frontal cortex contralateral to the hemicerebellectomy side received injections of anti-NMDA antibodies from patients affected by anti-NMDA encephalitis. In the compensated hemicerebellectomized rats, the frontal injections of anti-NMDA antibodies elicited a marked decompensation state characterized by slight worsening of the motor symptoms as well as severe impairment of spatial mnesic and procedural performances. Conversely, in the sham-operated group the frontal injections of anti-NMDA antibodies elicited slight motor and spatial impairment. The molecular analyses indicated that cerebellar compensatory processes were related to a relevant rearrangement of glutamatergic synapses (NMDA and AMPA receptors and other glutamatergic components) along the entire cortico-cerebellar network. The long-term maintenance of the rearranged glutamatergic activity plays a crucial role in the maintenance of recovered function.

Autoimmune atypical parkinsonism - A group of treatable parkinsonism.

BACKGROUND: Immunological causes of atypical parkinsonism/Parkinson plus syndromes are rare. OBJECTIVE: To study the clinical and laboratory features and treatment outcome of autoimmune atypical parkinsonism. METHODS: Retrospective case series. Patients with atypical parkinsonism and positive antibodies were identified retrospectively. Those who received immunotherapy (intravenous methyl prednisolone 1g daily for five days followed by mycophenylate mofetil 2g daily or azathioprine 2-3mg/kg/day) and consented for publication of non-anonymized videos were included. RESULTS: There were ten cases (nine males, age range 49-75years, disease duration 2months to 13years, follow-up 1-7months) of atypical parkinsonism [probable multiple system atrophy (MSA)-2, possible progressive supranuclear palsy (PSP)-1, probable PSP-3]. Eight had new uncharacterized neuronal antibodies, leucine rich glioma associated protein 1 (LGI1) antibody in one, and the other had another uncharacterized neuronal antibody along with LGI1 antibody. Four had abnormal CSF. There was a prompt, dramatic improvement in terms of Unified Parkinson Disease Rating Scale motor scale and or modified Rankin Scale as well as improvement in eye movement, postural instability, cerebellar, autonomic and non-motor symptoms. Two had reappearance of symptoms on discontinuing steroids and improvement on restarting. One died of infection despite good recovery of encephalopathy and parkinsonism. CONCLUSION: Autoimmune atypical parkinsonism is characterized by atypical parkinsonism with neuronal specific antibodies, sometimes associated with abnormal CSF and significant response to immunotherapy.

Anti-NMDA encephalitis: an uncommon, autoimmune mediated form of encephalitis.

We report an interesting case of a 19 year old female with findings on MRI suggestive of viral encephalitis. An extensive workup was negative for infectious causes and she was subsequently diagnosed with anti-NMDA encephalitis. Anti-NMDA encephalitis is a highly lethal but treatable form of autoimmune encephalitis that has recently been characterized. It is frequently found in young women and associated with an underlying teratoma. Although rare, this diagnosis should be considered in young females for whom a rapid onset of encephalitis cannot be explained by more common causes.

Nodding syndrome in Tanzania may not be associated with circulating anti-NMDA-and anti-VGKC receptor antibodies or decreased pyridoxal phosphate serum levels-a pilot study.

BACKGROUND: Nodding syndrome (NS) is a seemingly progressive epilepsy disorder of unknown underlying cause. We investigated association of pyridoxal-phosphate serum levels and occurrence of anti-neuronal antibodies against N-methyl-D-aspartate (NMDA) receptor and voltage gated potassium channel (VGKC) complex in NS patients. METHODS: Sera of a Tanzanian cohort of epilepsy and NS patients and community controls were tested for the presence of anti-NMDA-receptor and anti-VGKC complex antibodies by indirect immunofluorescence assay. Furthermore pyridoxal-phosphate levels were measured. RESULTS: Auto-antibodies against NMDA receptor or VGKC (LG1 or Caspr2) complex were not detected in sera of patients suffering from NS (n=6), NS plus other seizure types (n=16), primary generalized epilepsy (n=1) and community controls without epilepsy (n=7). Median Pyridoxal-phosphate levels in patients with NS compared to patients with primary generalized seizures and community controls were not significantly different. However, these median pyridoxal-phosphate levels are significantly lower compared to the range considered normal in Europeans. CONCLUSIONS: In this pilot study NS was not associated with serum anti-NMDA receptor or anti-VGKC complex antibodies and no association to pyridoxal-phosphate serum levels was found.

Encefalitis autoinmune reversible y anticuerpos anti-receptores de N-metil-D-aspartato: Report of one case / Limbic encephalitis with positive anti-N-methyl-D-aspartate antibodies

Background: Limbic encephalitis is a subacute syndrome characterized by memory impairment, confusion, seizures, hypothalamic dysfunction and psychiatric symptoms. It has been associated to tumors located outside of the central nervous system. In 2007, anti-N-methyl-D-aspartate receptors (NMDAr) antibodies were found in serum and CSF of patients with this particular type of encephalitis. We report a 25-year-old female who, following upper respiratory tract symptoms, developed serious behavioral and consciousness impairment that progressed to coma. Cerebrospinal fluid (CSF) analysis showed a lymphocyte pleocytosis, the electroencephalogram was altered with a slow encephalopathic rhythm and a brain magnetic resonance imaging was normal. Infectious etiologies were ruled out. CSF and serum anti NMDA receptors antibodies were positive.

[Limbic encephalitis with positive anti-N-methyl-D-aspartate antibodies. Report of one case]. / Encefalitis autoinmune reversible y anticuerpos anti-receptores de N-metil-D-aspartato.

BACKGROUND: Limbic encephalitis is a subacute syndrome characterized by memory impairment, confusion, seizures, hypothalamic dysfunction and psychiatric symptoms. It has been associated to tumors located outside of the central nervous system. In 2007, anti-N-methyl-D-aspartate receptors (NMDAr) antibodies were found in serum and CSF of patients with this particular type of encephalitis. We report a 25-year-old female who, following upper respiratory tract symptoms, developed serious behavioral and consciousness impairment that progressed to coma. Cerebrospinal fluid (CSF) analysis showed a lymphocyte pleocytosis, the electroencephalogram was altered with a slow encephalopathic rhythm and a brain magnetic resonance imaging was normal. Infectious etiologies were ruled out. CSF and serum anti NMDA receptors antibodies were positive.

[Action mechanism of adamantamines: do their activity on glutamatergic receptors intervene in the expression of their pharmacological profile?]. / Mécanisme d'action des adamantamines: leur activité sur les récepteurs glutamatergiques (NMDA) intervient-elle dans l'expression de leur profil pharmacologique?

Recent data on the aptitude of adamantamines to inhibit or to stimulate glutamatergic (NMDA) neuromediation, to display anti-GABAergic and antiglycinergic components (by blocking the Cl- channel), on the one hand, and on the opposition of the central glutamatergic and dopaminergic systems, on the other, could suggest that the glutamatergic (NMDA) or the anti-NMDA activity, exhibited by some adamantamines, could play an important role in the expression of their pharmacological profile. Anti-NMDA properties, for the adamantamines which exhibited them, could be, by themselves or by developing their anti-GABAergic or antiglycinergic components, the first cause of the hypermotility and dopaminomimetic activity induced by these molecules. Glutamatergic (NMDA) component, which could be displayed by some lipophilic or important steric obstruction on azote exhibiting adamantamines, could amplifie the excitating effects of their anti-GABAergic and antiglycinergic components on the limbic system's brain structures (hippocampus, amygdala) and could contribute to the exhibition of hypomotility, fright, agressivity and convulsions. According to these data, which must be amplier confirmed and deeped, it would be possible to envisage the improvement of adamantamines against the Parkinson's disease (when they exhibit anti-NMDA activity) or their use against the Alzheimer's disease and the late stages of the Parkinson's disease (when they exhibit NMDA activity).