The human globus pallidus internus is sensitive to rewards - Evidence from intracerebral recordings.

BACKGROUND: The globus pallidus internus (GPi) is the final output relay of the basal ganglia for the control of movements but has also been shown to belong to a second pathway projecting to the lateral habenula. This latter pathway is related to reward processing. METHOD: This prompted us to record, in eight patients receiving deep brain stimulation of the GPi for the alleviation of various movement disorders, local field potentials (LFP) while these patients performed a lottery task. The task entailed choosing between a higher and a lower number, which changed their color after the patient's choice with red (green) signaling a loss (win, in Euro cents) corresponding to the chosen number. RESULTS: Surface recordings showed a feedback related negativity from a frontal midline site, while time domain averages in the GPi showed differential modulation depending on the valence of the stimulus with polarity inversion indicating that this reward-modulated activity was indeed generated locally. Furthermore, wavelet decomposition of the LFP showed a reward-related response in the high beta/low gamma range. CONCLUSION: We conclude that human GPi is involved in reward processing, possibly in relation to the lateral habenula.

Importance of follow-up cerebrospinal fluid analysis in cryptococcal meningoencephalitis.

Cryptococcal meningoencephalitis represents a serious infection of the central nervous system, where reliable prognostic factors during the disease course are needed. Twenty-one patients diagnosed with cryptococcal meningoencephalitis in a German university hospital from 1999 to 2013 were analysed retrospectively. CSF parameters were analysed prior to therapy and during antifungal treatment and were compared between patients who survived or deceased. Fifteen patients clinically improved after antifungal therapy, while six patients died. No differences were observed between the outcome groups for the CSF parameters cell count, lactate, total protein, and CSF-serum albumin quotients (QAlb). Follow-up examinations of serum cryptococcal antigen titer and CSF cell count have shown that these parameters cannot be used to monitor the efficacy of antifungal therapy as well. In contrast, the course of QAlb during therapy was indicative for the outcome as a possible prognostic marker. In patients with clinical improvement QAlb values were falling under therapy, while rising QAlb values were found in patients with fatal outcome indicating a continuing dysfunction of the blood-CSF barrier. In conclusion, our results indicate that, among the various CSF parameters, the course of QAlb presents a promising marker that might be used to monitor the efficacy of antifungal therapy.

Fluorodeoxyglucose positron emission tomography (FDG-PET) is useful in the diagnosis of neurosarcoidosis.

A 45-year-old man presented with a progressive transverse spinal cord syndrome. MRI scanning revealed bitemporal and multiple spinal lesions with significant enhancement after gadolinium administration mimicking an acute disseminated encephalomyelitis. CSF analyses showed a lymphocytic pleocytosis. After treatment with high dose steroids clinical improvement was observed with a secondary decline shortly thereafter. MRI rescanning showed no remarkable alterations of the lesions. Further diagnostic work-up included a fluorodeoxyglucose positron emission tomography (FDG-PET) of the whole body to search for occult inflammation or neoplasia. The FDG-PET showed hypermetabolic foci corresponding to the lesions on MRI and additionally increased uptake in mediastinal and pulmonary hilar lymph nodes. A mediastinal lymph node was biopsied. Pathology was consistent with the diagnosis of sarcoidosis. The usual diagnostical tools to evaluate a sarcoidosis, such as serum angiotensin converting enzyme (ACE) and computed tomography of the chest were performed initially and revealed no pathological results. Therefore, in this case FDG-PET was crucial for the diagnostic work-up leading to an accessible inflammatory lesion outside the CNS for biopsy and the final diagnosis of sarcoidosis.

Vesicle associated membrane protein (VAMP)-7 and VAMP-8, but not VAMP-2 or VAMP-3, are required for activation-induced degranulation of mature human mast cells.

Mediator release from mast cells (MC) is a crucial step in allergic and non-allergic inflammatory disorders. However, the final events in response to activation leading to membrane fusion and thereby facilitating degranulation have hitherto not been analyzed in human MC. Soluble N-ethyl-maleimide-sensitive factor attachment protein receptors (SNARE) represent a highly conserved family of proteins that have been shown to mediate intracellular membrane fusion events. Here, we show that mature MC isolated from human intestinal tissue express soluble N-ethylmaleide sensitive factor attachment protein (SNAP)-23, Syntaxin (STX)-1B, STX-2, STX-3, STX-4, and STX-6 but not SNAP-25. Furthermore, we found that primary human MC express substantial amounts of vesicle associated membrane protein (VAMP)-3, VAMP-7 and VAMP-8 and, in contrast to previous reports about rodent MC, only low levels of VAMP-2. Furthermore, VAMP-7 and VAMP-8 were found to translocate to the plasma membrane and interact with SNAP-23 and STX-4 upon activation. Inhibition of SNAP-23, STX-4, VAMP-7 or VAMP-8, but not VAMP-2 or VAMP-3, resulted in a markedly reduced high-affinity IgE receptor-mediated histamine release. In summary, our data show that mature human MC express a specific pattern of SNARE and that VAMP-7 and VAMP-8, but not VAMP-2, are required for rapid degranulation.