Fulminant thymomatous AMPAR-antibody limbic encephalitis with hypertonic coma, bruxism, an isoelectric electroencephalogram and temporal cortical atrophy, with recovery.

Autoimmune encephalitides are a potentially devastating group of treatable disorders with a wide variety of clinical presentations. The most studied autoimmune encephalitis is caused by antibodies to the N-methyl-D-aspartate glutamate receptor. A rarer cause is due to antibodies against the evolutionarily related α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). The full assortment of electroencephalogram (EEG) and clinical descriptions of the latter are yet to be fully described. A 44-year-old woman with impaired consciousness and subsequent coma characterised by an isoelectric EEG was diagnosed with AMPAR-antibody limbic encephalitis. MRI revealed temporal T2 hyperintensities that improved with immunosuppression, although leaving marked cortical atrophy. Gradual clinical improvement saw the development of aggressive bruxism requiring botulinum toxin injection with eventual meaningful clinical recovery. This case expands the clinical spectrum of AMPAR limbic encephalitis to include aggressive bruxism, and highlights that despite poor clinical and EEG findings at the outset, recovery is still possible.

The impact of lymphopenia on delirium in ICU patients.

BACKGROUND: Immunosuppressed states may predispose patients to development of acute brain injury during times of critical illness. Lymphopenia is a non-specific yet commonly used bedside marker of immunosuppressed states. METHODS: We examined whether lymphopenia would predict development of acute brain dysfunction (delirium and/or coma) in 518 patients enrolled in the Bringing to Light the Risk Factors and Incidence of Neuropsychological Dysfunction in ICU Survivors (BRAIN-ICU) study in medical and surgical ICUs of a tertiary care, university-based medical center. Utilizing proportional odds logistic regression and Cox proportional hazards survival analysis, we assessed the relationship between pre-enrollment lymphocytes and subsequent cognitive outcomes including delirium- and coma-free days (DCFDs) and 30-day mortality. RESULTS: There were no statistically significant associations between lymphocytes and DCFDs (p = 0.17); additionally, the relationship between lymphocytes and mortality was not statistically significant (p = 0.71). Among 259 patients without history of cancer or diabetes, there was no statistically significant association between lymphocytes and DCFDs (p = 0.07). CONCLUSION: lymphopenia, a commonly used bedside marker of immunosuppression, does not appear to be a marker of risk for acute brain injury (delirium/coma) or 30-day mortality in general medical/surgical ICU patients.

Barbiturate coma may promote reversible bone marrow suppression in patients with severe isolated traumatic brain injury.

OBJECTIVES: Barbiturate coma is employed in brain-injured patients whenever increases in intracranial pressure remain unresponsive to less aggressive therapeutic regimens. Barbiturate-mediated neuroprotection, however, is weakened by an increased infection rate related to barbiturate-induced immunosuppression. Co-administration of barbiturates with antibiotics known to induce bone marrow suppression could, in turn, potentiate barbiturate-mediated immunosuppression. Adverse drug reactions and interactions of thiopental with antibiotics in terms of leukopenia, infection rate, and bone marrow suppression were investigated. METHODS: White blood cells were measured daily, tracheobronchial secretion and urine were examined for bacterial growth twice a week or if an infection was suspected. RESULTS: A total of 52 patients with severe isolated head injury were consecutively investigated. Due to increased intracranial pressure (ICP), which did not respond to analgosedation, barbiturate coma was performed in 23 cases. The other 29 patients remained analgosedated. Leukocytes and neutrophils were reversibly and significantly decreased in all patients, mostly sustained under thiopental. The pulmonary infection rate due to gram-negative organisms was nearly doubled during barbiturate coma. Reversible agranulocytosis and bone marrow suppression attributed to antibiotics developed in six patients after thiopental administration. Mortality rate, however, was not increased by these adverse effects. CONCLUSIONS: Barbiturate coma may cause reversible leukopenia and an increased infection rate. Long-term administration of thiopental may also promote reversible antibiotic-induced bone marrow suppression. The mechanisms and site of interaction between thiopental and antibiotics cannot be assessed by the present study and remain to be clarified. However, during and after barbiturate coma, close monitoring of leukocytes and infections and careful selection of antibiotics is required.

Cerebrospinal fluid levels of biopterin, nitric oxide metabolites, and immune activation markers and the clinical course of human cerebral malaria.

Cerebrospinal fluid samples from 130 children who presented with cerebral malaria were investigated to elucidate the impact of biopterin production, NO formation, and local immune activation on the clinical course of this disease. Biopterin levels were significantly lower in patients who were in a deeper coma (P = .02). Cerebrospinal fluid concentrations of NO were significantly higher in children who died than in survivors (P = .037); however, this was not the case for macrophage activation markers, neopterin, and soluble tumor necrosis factor receptor p75 (sTNFR-75). Biopterin, neopterin, and sTNFR-75 but not NO concentrations were significantly related to each other. Low biopterin levels in deep coma are compatible with an impaired local Th1 response, but the low levels could also be due to the scavenging of radicals or to decreased neurotransmitter synthesis. Local production of NO, most likely by nonimmune mechanisms, may be detrimental in cerebral malaria; however, this appears not to be the case for local Th1-mediated immune pathways.