Substantia nigra depigmentation and exposure to encephalitis lethargica.

OBJECTIVE: Parkinsonism has occasionally been reported as a consequence of infectious diseases. The present study examines the clinical and pathological correlates of parkinsonism across birth cohorts in relation to critical exposure to the encephalitis lethargica epidemic in the early 1900s. METHODS: The study population consisted of 678 participants in the Nun Study, of whom 432 died and came to autopsy. Qualitative indices of substantia nigra (SN) depigmentation were verified in a subset of 40 randomly selected subjects using quantitative stereological techniques. SN depigmentation, detected neuropathologically, was correlated with clinical parameters of Parkinson disease, age, and birth cohort. RESULTS: SN depigmentation was detected in 57 (13.2%) of the cohort. Although qualitative SN depigmentation correlated modestly with age (p = 0.02), it correlated best with birth cohort (p = 0.009) for women born in the years 1895-1899. Quantitative measures of SN depigmentation were increased in this birth cohort compared to age matched subjects from flanking birth cohorts 1890-1894 and 1900-1904 (p < 0.001). SN depigmentation correlated with speed of 6- and 50-foot walk (p < 0.0001), up and go test (p < 0.0001), and hand coordination (p < 0.0001). INTERPRETATION: Subjects in the birth cohort 1895-1899 would have been in their late teens and 20s at the onset and during the peak of the encephalitis lethargica epidemic. These were precisely the age ranges of persons who were most often affected by the illness. These data suggest the possibility that the coexistence of parkinsonism and SN depigmentation in this birth cohort may have resulted from the yet undetermined infectious agent responsible for encephalitis lethargica.

Inflammation-induced lethargy is mediated by suppression of orexin neuron activity.

In response to illness, animals subvert normal homeostasis and divert their energy utilization to fight infection. An important and unexplored feature of this response is the suppression of physical activity and foraging behavior in the setting of negative energy balance. Inflammatory signaling in the hypothalamus mediates the febrile and anorectic responses to disease, but the mechanism by which locomotor activity (LMA) is suppressed has not been described. Lateral hypothalamic orexin (Ox) neurons link energy status with LMA, and deficiencies in Ox signaling lead to hypoactivity and hypophagia. In the present work, we examine the effect of endotoxin-induced inflammation on Ox neuron biology and LMA in rats. Our results demonstrate a vital role for diminished Ox signaling in mediating inflammation-induced lethargy. This work defines a specific population of inflammation-sensitive, arousal-associated Ox neurons and identifies a proximal neural target for inflammatory signaling to Ox neurons, while eliminating several others.

Fatal rectal perforation following boar-to-boar mounting.

Although abnormal sexual behavior, including boar-to-boar mounting with anal penetration, is recognized in pubescent pigs, reports of the pathologic consequences are scarce. A 7-month-old male minipig, housed with age-matched males, died within 1 day of the onset of lethargy and reluctance to rise. At necropsy, 2 rectal tears were identified as the cause for fibrinous peritonitis, and spermatozoa were identified in the pelvic and peritoneal cavity by light and transmission electron microscopy. According to DNA typing results, using 11 porcine microsatellites, the intraperitoneal semen was from at least 2 pen mates. The prohibition of castration of fattening pigs, implemented or planned in multiple European countries, could increase the risk of rectal perforation in co-housed pigs.

Neuroanatomical correlates of neuropsychiatric symptoms in Alzheimer's disease.

Alzheimer's disease research has largely concentrated on the study of cognitive decline, but the associated behavioural and neuropsychiatric symptoms are of equal importance in the clinical profile of the disease. There is emerging evidence that regional differences in brain atrophy may align with variant disease presentations. The objective of this study was to identify the regions of decreased grey matter (GM) volume which were associated with specific neuropsychiatric behaviours in patients with mild Alzheimer's disease. Voxel-based morphometry was used to correlate GM derived from T(1)-weighted MRI images of 31 patients with mild Alzheimer's disease and specific neuropsychiatric symptoms and behaviours measured by the Neuropsychiatric Inventory. Delusions were associated with decreased GM density in the left frontal lobe, in the right frontoparietal cortex and in the left claustrum. Apathy was associated with GM density loss in the anterior cingulate and frontal cortex bilaterally, the head of the left caudate nucleus and in bilateral putamen. Agitation was associated with decreased GM values in the left insula, and in anterior cingulate cortex bilaterally. Neuropsychiatric symptoms of Alzheimer's disease seem to associate with neurodegeneration of specific neural networks supporting personal memory, reality monitoring, processing of reward, interoceptive sensations and subjective emotional experience. The study of neurodegenerative disorders such as Alzheimer's disease using voxel-based morphometry and other imaging modalities may further the understanding of the neural structures that mediate the genesis of abnormal behaviours.

Outcome of herpes simplex encephalitis in children.

BACKGROUND AND PURPOSE: Herpes simplex encephalitis (HSE) can cause high mortality and morbidity in children. Since local data of HSE in children are rare, we performed a retrospective study to evaluate the prognostic factors and outcome of HSE in Taiwan. METHODS: Children were enrolled into this study if they were diagnosed as having encephalitis and also had positive polymerase chain reaction for herpes simplex virus (HSV) from cerebrospinal fluid, and/or positive immunoglobulin M or at least four-fold elevation of immunoglobulin G against HSV type 1 or type 2 from serum during the period from December 1, 1984 to January 31, 2003. RESULTS: Forty patients were enrolled in this study. Twenty six patients (65%) had good outcome and 14 (35%) had poor outcome. No mortality or recurrence was found. Three-fifths of the patients were between 1 year and 6 years of age. Fever (75%) was the most common finding at admission, followed by seizures (63%), lethargy (60%), and altered consciousness (48%). Seizure and lethargy at the time of admission were more common in the poor outcome group (71% vs 58% and 64% vs 58%). Abnormal computed tomography/magnetic resonance imaging findings were found in 63% of patients in whom the examinations were performed. Abnormal electroencephalogram (EEG) findings were noted in 79% of tested patients. Acyclovir was used to treat 29 patients (73%). Abnormal neuroimaging or EEG findings were more prevalent in patients with poor outcome (75% vs 55% and 92% vs 71%), as well as delayed (>/=3 days) initiation of acyclovir therapy (92% vs 71%). There was no significant difference between the poor and good outcome groups in gender, age distribution, and clinical presentation. CONCLUSION: As we cannot predict the outcome of patients with HSE in the early beginning of illness and delay of treatment may cause disaster, early diagnosis and prompt acyclovir initiation are important requirements for successful management.

Neuroinvasive influenza virus A(H5N8) in fattening ducks, Hungary, 2015.

Highly pathogenic avian influenza (HPAI) A virus H5N8 was detected in far east Asian countries during 2014 and emerged in late 2014 in European countries. Hungary reported a HPAI A(H5N8) outbreak during late winter of 2015 at a Pekin duck fattening facility. Epidemiologic monitoring was extended to holdings in neighboring areas and nearby habitats used by wild birds but failed to identify the source of infection. In addition to respiratory symptoms, the affected birds showed lethargy and neuronal signs, including torticollis. Consistent with this finding, influenza A virus antigen was detected in large quantity in the brain. Molecular analysis of the identified strain showed very close genetic relationship (and >99% nucleotide sequence identity) with co-circulating HPAI A(H5N8) strains. A number of unique or rarely detected amino acid changes was detected in the HA (T220I, R512G), the M2 (I39M), the NA (T211I), the NS1 (P85T), and the PB2 (I261V) proteins of the Hungarian strain. Further studies are needed to demonstrate whether any of these mutations can be linked to neuroinvasiveness and neurovirulence in ducks.