White and Gray Matter Abnormalities in Manifest Huntington's Disease: Cross-Sectional and Longitudinal Analysis.

BACKGROUND AND PURPOSE: Early white matter (WM) changes and cortical atrophy in Huntington's disease (HD) are often evident before disease onset and extend through the brain during manifest stages. The trajectory of these brain abnormalities in symptomatic stages remains relatively unexplored. The aim of this study is to investigate how the pattern of WM and gray matter (GM) alterations progress over time. METHODS: We investigated alterations in brain WM, cortical thickness, and subcortical structures using diffusion and structural magnetic resonance imaging, in manifest HD patients (n = 13) compared to age-matched healthy controls (n = 11). Imaging and clinical data for the HD group were collected at follow-up (7 months) to explore possible longitudinal changes. RESULTS: Cross-sectional analyses identified significant posterior cortical thinning (P < .05) and symmetric fractional anisotropy (FA) reduction (P < .01) in brain WM of HD group compared to HC. These changes were strongly correlated with impairment in motor symptoms and processing speed. Subcortical atrophy was significant in caudate, putamen, globus pallidus, and thalamus (P < .001). Regions of interest analysis revealed a significant reduction in FA of the corpus callosum (CC) (-2.19%, P < .05) upon follow-up, whereas no significant cortical thinning and subcortical atrophy was found. CONCLUSIONS: This study showed broad GM and WM abnormalities in manifest HD patients. Reductions in FA and cortical thinning correlated significantly with the disturbances of motor and cognitive processing that describe HD. Follow-up assessment showed that the CC is compromised in the absence of detectable GM changes or motor decline, suggesting it plays an important role in disease progression.

Anti-glutamic acid decarboxylase antibody (GAD) syndromes may have more aggressive disease course in African Americans and early onset of presentation compare to Caucasians group.

Anti-Glutamic acid decarboxylase antibodies (GAD) are increasingly diagnosed in the clinic and this antibody related syndromes can manifest commonly as autoimmune encephalitis, Stiff person syndrome and cerebellar ataxia. However, it is unclear if the race has role in age of incidence, presentation and severity of symptoms of anti-GAD associated conditions. In our cohort of 40 patients who were anti-GAD positive, we observed that the age at which the anti-GAD titers turned out to be positive was significantly lower in African Americans (AA) compared to Caucasians (Cau) irrespective of the type of conditions. However, the age at symptoms onset didn't differ significantly different between these groups. Furthermore, AA anti-GAD positive patients had seizures as their initial presentation that was significantly higher in incidence compared to Cau indicating that AA have more aggressive form of autoimmune phenomenon for reasons unknown. Future studies to explore the variations in autoimmune process and their phenotypes may aid in understanding anti-GAD syndromes differently between these racial groups.

Varicella zoster encephalitis in an immunocompromised patient presented with migraine type headache: A case report.

Varicella zoster virus (VZV) has been increasingly linked with encephalitis and atypical presentations in immunosuppressed patients. We present a patient with history of immunosuppressant intake for polymyositis who initially presented with throbbing frontal headache that raised the suspicion of migraine. She did not respond to anti-migraine medication and later developed stimulus induced myoclonus. She then had significant neurological decline and eventually became encephalopathic. Her initial imaging of brain was unremarkable which warranted further investigations. She was then diagnosed to be VZV positive in the cerebrospinal fluid (CSF) sample that confirmed VZV encephalitis. She responded well to IV Acyclovir treatment and her neurological function improved significantly. In this case, there was delay in diagnosis of VZV in the setting of immunosuppression and non-specific clinical presentation. Therefore, we encourage to strongly consider early VZV diagnostic work up and treatment in immunocompromised patients who can present with non-specific symptoms without a typical cutaneous rash.

Determination of serum aflatoxin B1-lysine to evaluate the efficacy of an aflatoxin-adsorbing feed additive in pigs fed an aflatoxin B1-contaminated diet.

In this study, serum aflatoxin B1 (AFB1)-lysine was determined in order to evaluate the in vivo efficacy of a hydrated sodium calcium aluminosilicate (HSCAS) in pigs fed AFB1. Twenty-four 49-day-old crossbred barrows were maintained in individual cages and allowed ad libitum access to feed and water. A completely randomized design was used with six animals assigned to each of four dietary treatments for 21 days as follows: (A) basal diet (BD), (B) BD supplemented with 0.5 % HSCAS, (C) BD supplemented with 1.1 mg/kg AFB1, and (D) BD supplemented with 0.5 % HSCAS and 1.1 mg/kg AFB1. HSCAS was able to alleviate the toxic effects of AFB1 on pigs and reduce (P < 0.05) the levels of serum AFB1-lysine. Cumulative reductions of adduct yield values, calculated through the equation [(pg AFB1-lysine/mg albumin) / (µg AFB1/kg body weight)], were 53.0, 62.8, and 72.1 after 7, 14, and 21 days of oral exposure, respectively. AFB1-lysine has potential as an AFB1-specific biomarker for diagnostic purposes and for evaluating the efficacy of chemoprotective interventions in pigs.

Pleural Lymphoma Presenting as Chylothorax.

Pleural disease in Non-Hodgkin's Lymphoma is well documented and commonly presents with pleural effusion in 20% of patients. However, solid pleural involvement is less common and is usually a secondary event. Primary pleural lymphomas are extremely rare. Hereby we report a rare case of primary pleural lymphoma presenting as chylothorax.

Wegener's Granulomatosis: Are We Still Missing It?

We report the case of an 18-year-old female who was mis-diagnosed as a smear-negative pulmonary tuberculosis and advised standard antituberculosis treatment. She later presented with clinio-radiological worsening and thrombosis of superficial veins of the lower extremity. Cytoplasmic anti-neutrophil cytoplasmic antibody and computed tomography-guided lung biopsy confirmed the diagnosis of Wegener's granulomatosis. The rare association of superficial vein thrombosis with lung manifestation is highlighted here as also the need for a high index of clinical suspicion to avoid a missed or delayed diagnosis.

Longitudinal study of the substantia nigra in Parkinson disease: A high-field (1) H-MR spectroscopy imaging study.

INTRODUCTION: The value of biomarkers in early diagnosis and development of therapeutics in Parkinson's disease (PD) is well established. METHODS: We used proton magnetic resonance spectroscopy in a prospective, longitudinal study of 23 patients with early PD, naïve to dopaminergic therapy, and six age-matched healthy controls to examine the temporal changes in metabolic profile of substantia nigra over a period of 3 months. RESULTS: N-acetyl aspartate to creatine ratio at month 3 was compared with baseline values in the PD and control groups, as well as the side-to-side difference of the ratio at baseline. By month 3, n-acetyl aspartate to creatine ratio had decreased by 4.4% in patients with PD (P = 0.024), without a concomitant change in healthy controls. The side-to-side asymmetry was significantly higher in the PD group (16.7%) vs. healthy controls (1.6%, P = 0.0024). CONCLUSION: Estimation of change in the n-acetyl aspartate to creatine ratio appears to be a fast, quantifiable, and reliable marker of dopaminergic neuronal viability in PD.

Characterization of retinal architecture in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is a neurodegenerative disorder associated with dopaminergic cell loss and α-synuclein aggregation in Lewy bodies, which has been demonstrated in the retina. METHODS: We performed a spectral-domain optical coherence tomography (OCT) study in patients with PD and healthy controls to measure the peripapillary retinal nerve fiber layer thickness and macular volume. Intra-retinal segmentation was performed to measure the volume of the retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL), and outer nuclear (ONL) layers. Analysis was carried out blinded to the clinical status of study participants. RESULTS: 101 PD and 46 healthy control eyes were included in the study. In PD patients, peripapillary retinal nerve fiber layer was not significantly thinner (96.95 µm vs 94.42 µm, p=0.08) but macular volume was (8.58 mm3 vs 8.33 mm3, p=0.0002). Intra-retinal segmentation showed that PD subjects have reduced GCL, IPL, INL and ONL volumes. In contrast, the OPL volume was significantly increased (0.81 mm3 vs 0.78 mm3 p=0.0214). CONCLUSIONS: Thickening of the OPL is a novel finding which may correspond to the localization of α-synuclein in the OPL of PD patients. We hypothesize that the enlargement of the OPL may represent a potential biomarker of α-synuclein aggregation in PD. This may have significant clinical implications.

A prospective cohort study of the effects of lower extremity orthopaedic surgery on outcome measures in ambulatory children with cerebral palsy.

BACKGROUND: Lower-extremity musculotendinous surgery is standard treatment for ambulatory children with deformities such as joint contractures and bony torsions resulting from cerebral palsy (CP). However, evidence of efficacy is limited to retrospective, uncontrolled studies with small sample sizes focusing on gait variables and clinical examination measures. The aim of this study was to prospectively examine whether lower-extremity musculotendinous surgery in ambulatory children with CP improves impairments and function measured by gait and clinical outcome tools beyond changes found in a concurrent matched control group. METHODS: Seventy-five children with spastic CP (Gross Motor Function Classification System levels I to III, age 4 to 18 y) that underwent surgery to improve gait were individually matched on the basis of sex, Gross Motor Function Classification System level, and CP subtype to a nonsurgical cohort, minimizing differences in age and Gross Motor Function Measure Dimension E. At baseline and at least 12 months after baseline or surgery, participants completed gait analysis and Gross Motor Function Measure, and parents completed outcome questionnaires. Mean changes at follow-up were compared using analysis of covariance adjusted for baseline differences. RESULTS: Surgery ranged from single-level soft tissue release to multilevel bony and/or soft tissue procedures. At follow-up, after correcting for baseline differences, Gillette Gait Index, Pediatric Outcomes Data Collection Instrument Expectations, and Pediatric Quality of Life Inventory (PedsQL) Physical Functioning improved significantly for the surgical group compared with the nonsurgical group, which showed minimal change. CONCLUSIONS: On the basis of a matched concurrent data set, there was significant improvement in function after 1 year for a surgical group compared with a nonsurgical group as measured by the Gillette Gait Index, with few significant changes noted in outcome measures. Changes over 1 year are minimal in the nonsurgical group, supporting the possibility of ethically performing a randomized controlled trial using nonsurgical controls. LEVEL OF EVIDENCE: Therapeutic level 2. Prospective comparative study.

Periodic alternating nystagmus and periodic alternating skew deviation in spinocerebellar ataxia type 6.

The combination of periodic alternating nystagmus (PAN) and periodic alternating skew deviation (PASD) is rare. We report a case of PAN and PASD in a patient with spinocerebellar ataxia type 6 (SCA-6) and discuss the role of the cerebellum as a plausible mechanism for this combined pathologic condition.

Stalking and Huntington's disease: a neurobiological link?

This case report describes a patient with Huntington's Disease (HD) who allegedly stalked her therapist. The patient developed recurrent thoughts about her therapist as well as amorous feelings towards her therapist. She engaged in stalking behavior including unwelcome gifts, multiple telephone calls to the therapist's office and home, and making threats towards the therapist. The patient continued to contact the therapist after the therapist filed a Personal Protection Order. The patient was successfully treated with risperidone and fluvoxamine. Through a focused review of the relevant literature, the authors explore the potential relationship between the patient's obsessional thoughts, amorous feelings towards her therapist, the basal ganglia dysfunction, and the stalking behavior. The authors posit a hypothesis of stalking as a novel early manifestation of HD in this patient. To the best of the authors' knowledge, this is the first reported case of stalking occurring with potentially causal organic lesions.

Protection of mature oligodendrocytes by inhibitors of caspases and calpains.

Mature mouse oligodendrocytes (OLs) are susceptible to death in demyelinating diseases such as multiple sclerosis and in brain injury following neurotrauma, ischemia, or stroke. To understand mechanisms leading to death of mature OLs and develop strategies for protection, we utilized cultures of mature mouse OLs to investigate the role of caspases and calpains in OL cell death mediated by different mechanisms. The agents used were (i) staurosporine, which induces apoptotic death via inhibition of protein kinases; (ii) kainate, which activates non-NMDA glutamate receptors; (iii) thapsigargin, which releases intracellular calcium stores; and (iv) SNAP, which releases active NO species and causes necrotic cell death. Inhibitors blocking primary effector caspases (including caspase 3), the FAS (death receptor)-mediated initiator caspases (including caspase 8), and stress-induced caspases (including caspase 9), were tested for their protective effects. Inhibition of caspases 3, 8, and 9 each robustly protected OLs following insult with staurosporine, thapsigargin, or kainate when added at optimal times. The time of addition of the inhibitors for maximal protection varied with the agent, from 1 h of preincubation before addition of staurosporine to 6 h after addition of kainate. Much less protection was seen for the NO generator SNAP under any condition. The role of calcium in OL death in each model was investigated by chelating extracellular Ca++ with EGTA, and by inhibiting the Ca++-activated calpain proteases. Calcium chelation did not protect against staurosporine, but decreased OL death initiated by kainate, thapsigargin, or NO. The calpain inhibitors PD150606 and calpain inhibitor I protected from cell death initiated by staurosporine, kainate, and thapsigargin, but not from cell death initiated by the NO donor SNAP.