Hearing impairment in Parkinson's disease: Expanding the nonmotor phenotype

The objective of this study was to evaluate hearing impairment in patients affected by Parkinson's disease compared with hearing scores observed in normal age‐ and sex‐matched controls. One hundred eighteen consecutive patients with a clinical diagnosis of Parkinson's disease were screened. Severity of motor symptoms and staging were measured with the Unified Parkinson's Disease Rating Scale (section III) and the Hoehn and Yahr scale. Audiometric evaluation consisted of a comprehensive audiologic case history and questionnaire, visual otoscopic examination, acoustic immittance measures (tympanogram and acoustic reflexes), pure tone audiometry, and measurement of brain stem auditory‐evoked potentials. Healthy age‐ and sex‐matched subjects were selected as the control group. One hundred six of 118 patients were enrolled. Pure tone audiometry revealed age‐dependent high‐frequency hearing loss in patients with Parkinson's disease compared with both normative values and values for healthy age‐ and sex‐matched controls (75/106 [71%], χ² = 5.959, P = .02; 92/106 [86.8%] vs 60/106 [56.6%], χ² = 23.804, P < .001, respectively). Pure tone audiometry scores correlated with Hoehn and Yahr scale scores (P < .05). Brain stem auditory‐evoked potentials were normal in all patients. Our patients with Parkinson's disease showed age‐dependent peripheral, unilateral, or bilateral hearing impairment. Whether these auditory deficits are intrinsic to Parkinson's disease or secondary to a more complex impaired processing of sensorial inputs occurring over the course of illness remains to be determined. Because α‐synuclein is located predominately in the efferent neuronal system within the inner ear, it could affect susceptibility to noise‐induced hearing loss or presbycusis. It is feasible that the natural aging process combined with neurodegenerative changes intrinsic to Parkinson's disease might interfere with cochlear transduction mechanisms, thus anticipating presbycusis. © 2012 Movement Disorder Society     

Prefrontal cortex controls human balance during overground ataxic gait

Purpose: 1) to verify if prefrontal cortex (PFC) is activated during over ground walking in ataxic patients, 2) to correlate the clinical parameters of gait with the PFC activation patterns. Methods: Fourteen patients and 20 healthy subjects were studied. Ataxia was assessed by the Scale for the Assessment and Rating of Ataxia (SARA). A 2-channel near-infrared system was used to investigate the changes in oxygenated ([O2Hb]t) and deoxygenated ([HHb]t) hemoglobin concentrations on the PFC during gait. [O2Hb] baseline-corrected activation values ([O2Hb]c) were calculated by the difference between [O2Hb]t and [O2Hb] during upright posture ([O2Hb]b). Results: [O2Hb]t was increased for both channels (respectively p < 0.01 and p = 0.01) only in the patients. No variation was observed in [HHB]t. The correlation coefficient between [O2Hb]c and the SARA gait score was respectively r: 0.878 (p < 0.01) and r: 0.839 (p < 0.01) for the right and left PFC, between [O2Hb]c and the SARA stance score respectively r: 0.893 (p < 0.01) and r: 0.832 (p < 0.01). Conclusions: During over ground gait PFC is bilaterally activated in patients with severe chronic ataxia. These findings may be associated with compensatory mechanisms which are involved in severe conditions when other nervous centers controlling balance are functionally not efficient.     

Progression of coronary artery calcium in men affected by human immunodeficiency virus infection

Cardiovascular risk is increased in HIV infected patients. We assessed progression of coronary artery calcium (CAC) in patients with HIV infection to identify factors that may help explain progression of atherosclerosis. Prospective, observational study of 132 HIV-infected men receiving chronic antiretroviral therapy (ART); we measured traditional atherosclerosis risk factors and assessed progression of CAC on sequential 64-slice CT scans at an average interval of 11 months (range 6-36). CAC score progression was defined as absolute and percentage change from baseline. During follow-up 45 patients (34%) showed absolute progression of CAC and 34 of them showed >15% yearly progression, a threshold previously associated with a high risk of myocardial infarction. Age, LDL cholesterol, visceral abdominal fat and current T-helper (CD4+) cell count were significantly associated with absolute CAC progression. Progression of subclinical atherosclerosis in HIV patients is associated with traditional coronary risk factors as well as HIV related factors such as the CD4+ cell count. Therefore, immunologic perturbations secondary to HIV infection may contribute to atherosclerosis progression.     

Ictal haemodynamic changes in a patient affected by “subtle” Epilepsia Partialis Continua

We report on a 64 year-old woman presenting with Epilepsia Partialis Continua (EPC) affecting the left hand since the age of 24 without neurological deficit. Structural MRI showed a region of focal cortical dysplasia (FCD) over the right central gyrus and lesions in the mesial frontal and occipital cortex secondary to perinatal hypoxic injury. Ictal spike haemodynamic mapping using simultaneous EEG-fMRI revealed significant BOLD signal changes prominent in the region of FCD (larger cluster), occipital cortex (global statistical maximum), prefrontal cortex and cerebellum. The cluster over FCD was in good agreement with the result of EEG source analysis.Our findings provide an interesting illustration of the ability of EEG-fMRI to reveal epileptogenic networks confirming the intrinsic epileptogenic properties of dysplastic neurons.     

An assessment of enteric nervous system and estroprogestinic receptors in obstructed defecation associated with rectal intussusception

Background The pathophysiological basis of obstructed defecation (OD) is still incompletely understood. In particular, few or no data are available concerning the enteric nervous system (ENS) in this condition. We investigated ENS abnormalities in patients with OD, undergoing surgery, together with the presence of estrogen (α and β) and progesterone receptors, and compare the results with those obtained in controls. Methods Full‐thickness rectal samples were obtained from 17 patients undergoing stapled transanal rectal resection for OD associated with rectal intussusception. Samples were analyzed by immunohistochemistry for enteric neurons, enteric glial cells, interstitial cells of Cajal (ICC), and for estrogen and progesterone receptors. Data were compared with those obtained in 10 controls. Key Results No differences between patients and controls were found for enteric neurons, whereas (compared with controls) OD patients displayed a significant decrease of enteric glial cells in both the submucous (P = 0.0006) and the myenteric (P < 0.0001) plexus. ICC were significantly increased in patients in the submucosal surface (P < 0.0001) and the myenteric area (P < 0.0001). Concerning estroprogestinic receptors, both were present on ICC in patients and controls. Estrogen receptors α and progesterone receptors were absent on enteric neurons and enteric glial cells in patients and controls, whereas estrogen receptors β were present in all controls and in 69% of patients’ enteric neurons (P = 0.18) and in 12% of patients’ glial cells (P = 0.0001). Conclusions & Inferences Patients with OD associated to rectal intussusception display abnormalities of the ENS and of estrogen receptors β.     

Electrophysiological, Morphological, and Topological Properties of Two Histochemically Distinct Subpopulations of Cerebellar Unipolar Brush Cells

Unipolar brush cells (UBCs) are excitatory cerebellar granular layer interneurons whose brush-like dendrites receive one-to-one mossy fiber inputs. Subclasses of UBCs differ primarily by expressing metabotropic glutamate receptor (mGluR) 1α or calretinin. We used GENSAT Tg(Grp-EGFP) BAC transgenic mice, which selectively express enhanced green fluorescent protein (EGFP) in mGluR1α-positive UBCs to compare the functional properties of the two subclasses. Compared to EGFP-negative UBCs, which include the calretinin-positive cells, EGFP-positive UBCs had smaller somata (area 48 vs 63 μm²), lower specific membrane resistance (6.4 vs. 13.7 KΩ cm²), were less prone to intrinsic firing, and showed more irregular firing (in cell-attached ~49 % were firing vs. ~88 %, and the CV was 0.53 vs. 0.32 for EGFP-negative cells). Some of these differences are attributable to higher density of background K⁺ currents in EGFP-positive cells (at ?120 mV, the barium-sensitive current was 94 vs. 37 pA in EGFP-negative cells); Ih, on the contrary, was more abundantly expressed in EGFP-negative cells (at ?140 mV, it was ?122 vs. ?54 pA in EGFP-positive neurons); furthermore, while group II mGluR modulation of the background potassium current in EGFP-negative UBCs was maintained after intracellular dialysis, mGluR modulation in EGFP-positive UBCs was lost in whole-cell recordings. Finally, cell-attached firing was reversibly abolished by the GABA_B activation in EGFP-positive, but not in EGFP-negative UBCs. Immunohistochemistry showed that EGFP-negative UBCs express GIRK2 at high density, while mGluR1α UBCs are GIRK2 negative, suggesting that GIRK2 mediates the mGluR-sensitive current in EGFP-negative UBCs. These data suggest that the two subclasses perform different functions in the cerebellar microcircuits.     

Pain in Amyotrophic Lateral Sclerosis: a psychological perspective

Pain in Amyotrophic Lateral Sclerosis is often underestimated and untreated by clinicians and few studies have investigated its specific features and impact. Pain experience was investigated with the Italian Questionnaire of Pain, together with the McGill Quality of Life Questionnaire for quality of life (QoL), at a baseline and at a 4-month follow-up. About half of ALS patients reported pain, described as nagging, sore, annoying, boring and exhausting, with periodic but enduring episodes. Pain was related with QoL and its intensity was able to predict QoL worsening. Obtained results indicate the importance of clinical investigation of pain in ALS patients and of the intervention with anti-pain treatment whenever necessary.