Alaina Borden

Increased blood-brain barrier permeability on perfusion computed tomography predicts hemorrhagic transformation in acute ischemic stroke.

Background/Purpose: Perfusion computed tomography (CT) is capable of measuring the permeability surface product (PS). PS reflects the permeability of the blood-brain barrier, involved in the pathophysiology of hemorrhagic transformation (HT) of ischemic stroke. The aim of our study was to determine if an increased PS can predict HT. Methods: A total of 86 patients with ischemic stroke were included. They underwent multimodality CT, including the measurement of PS. We compared the clinical and radiological characteristics of patients who developed HT to those who did not, using univariate analysis. Multivariate regression analyses were then used to determine HT predictors. Results: HT was observed in 27 patients (31%). Infarct PS was significantly associated with HT (p = 0.047), as were atrial fibrillation (p = 0.03), admission National Institute of Health Stroke Scale score (p = 0.02), infarct volume (p = 0.0004), presence of large-vessel occlusion (p = 0.0005) and a poorer collateral status (p = 0.003). Using logistic regression modeling, an infarct PS >0.84 ml/100 g/min was an independent predictor of HT (OR 28, 95% CI 1.75-452.98; p = 0.02). Other independent predictors of HT were infarct volume and a history of atrial fibrillation. Conclusions: Our findings suggest that infarct PS can be a predictor of HT and may help clinicians to improve patient care around thrombolysis decisions in the acute phase of ischemic stroke.

Post-Operative Edema Surrounding the Electrode: An Unusual Complication of Deep Brain Stimulation.

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Seizures in dominantly inherited Alzheimer disease

Objective: To assess seizure frequency in a large French cohort of autosomal dominant early-onset Alzheimer disease (ADEOAD) and to determine possible correlations with causative mutations. Methods: A national multicentric study was performed in patients with ADEOAD harboring a pathogenic mutation within PSEN1, PSEN2, APP, or a duplication of APP, and a minimal follow-up of 5 years. Clinical, EEG, and imaging data were systematically recorded. Results: We included 132 patients from 77 families: 94 PSEN1 mutation carriers (MCs), 16 APP duplication carriers, 15 APP MCs, and 7 PSEN2 MCs. Seizure frequency was 47.7% after a mean follow-up of 8.4 years (range 5–25). After 5-year follow-up and using a Cox model analysis, the percentages of patients with seizures were respectively 19.1% (10.8%–26.7%) for PSEN1, 28.6% (0%–55.3%) for PSEN2, 31.2% (4.3%–50.6%) for APP duplications, and no patient for APP mutation. APP duplication carriers showed a significantly increased seizure risk compared to both APP MCs (hazard ratio [HR] = 5.55 [95% confidence interval 1.87–16.44]) and PSEN1 MCs (HR = 4.46 [2.11–9.44]). Among all PSEN1 mutations, those within the domains of protein hydrophilic I, transmembrane II (TM-II), TM-III, TM-IV, and TM-VII were associated with a significant increase in seizure frequency compared to other domains (HR = 4.53 [1.93–10.65], p = 0.0005). Conclusions: Seizures are a common feature of ADEOAD. In this population, risk was significantly higher in the APP duplication group than in all other groups. Within PSEN1, 5 specific domains were associated with a higher seizure risk indicating specific correlations between causative mutation and seizures.

Decline in Verbal Fluency After Subthalamic Nucleus Deep Brain Stimulation in Parkinson's Disease: A Microlesion Effect of the Electrode Trajectory?

BACKGROUND Decline in verbal fluency (VF) is frequently reported after chronic deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson disease (PD). OBJECTIVE We investigated whether the trajectory of the implanted electrode correlate with the VF decline 6 months after surgery. METHODS We retrospectively analysed 59 PD patients (mean age, 61.9 ± 7; mean disease duration, 13 ± 4.6) who underwent bilateral STN-DBS. The percentage of VF decline 6 months after STN-DBS in the on-drug/on-stimulation condition was determined in respect of the preoperative on-drug condition. The patients were categorised into two groups (decline and stable) for each VF. Cortical entry angles, intersection with deep grey nuclei (caudate, thalamic or pallidum), and anatomical extent of the STN affected by the electrode pathway, were compared between groups. RESULTS A significant decline of both semantic and phonemic VF was found after surgery, respectively 14.9% ± 22.1 (P < 0.05) and 14.2% ± 30.3 (P < 0.05). Patients who declined in semantic VF (n = 44) had a left trajectory with a more anterior cortical entry point (56 ± 53 versus 60 ± 55 degree, P = 0.01) passing less frequently trough the thalamus (P = 0.03). CONCLUSIONS Microlesion of left brain regions may contribute to subtle cognitive impairment following STN-DBS in PD.

Psychosis revealing familial idiopathic basal ganglia calcification

We describe the case of a 39-year-old woman presenting with auditory hallucinations and delusions responsive to antipsychotic drugs. Computerized tomography scans revealed basal ganglia calcifications in the proband and in her two asymptomatic parents. Extensive etiological clinicobiological assessment allowed us to exclude known causes of brain calcifications and diagnose familial idiopathic basal ganglia calcification (IBGC). Neurological symptoms associated with psychiatric symptoms are common in IBGC. Nevertheless, purely psychiatric presentations, as demonstrated by the present case, are possible. However, a fortuitous association between asymptomatic IBGC and schizophrenia cannot be ruled out. Only brain imaging, followed by an extensive etiological assessment, allows for diagnosis of this rare disorder.

Non-motor fluctuations in Parkinson's disease: prevalence, characteristics and management in a large cohort of parkinsonian outpatients.

OBJECTIVE To describe demographic and clinical characteristics in a group of Parkinsons disease (PD) patients with non-motor fluctuations (NMF) and to evaluate the management of medications proposed to treat NMF. METHODS Three hundred and three PD patients (mean age, 66 ± 10.3 years; mean disease duration, 10.1 ± 6.5 years) were enrolled. Each patient was interviewed in a non-directed fashion about the main NMF manifestations, i.e. dysautonomic, mental, and sensory symptoms. Both groups of patients with and without NMF were compared. Dysautonomia, motor fluctuations, age, disease duration, and LEDD were included in a multiple regression to determine which were predictive of NMF. RESULTS NMF were found in 57 (19%) patients, mean age 65 ± 10.1 years, mean age at onset of PD 53.7 ± 10.9 years, mean disease duration 12.5 ± 6.9 years. NMF occurred on average 9.8 ± 7.7 years after the onset of PD. Fifty patients (86%) with NMF had also MF and 10 (21%) had PDD. Twenty-five (44%) patients suffered from sensory, 28 (49%) from autonomic and 25 (44%) from neuropsychiatric symptoms. Both disease and L-Dopa treatment durations, and LEDD were significantly higher in NMF patients group. Motor fluctuations (p = 0.0016) and presence of dysautonomia (p = 0.007) were found to be two independent predictors of NMF. CONCLUSION The development of new instruments to assess NMF is crucial for optimized management of advanced PD.

Acute genital pain during non-motor fluctuations improved by apomorphine

Unit of Occupational Rehabilitation and Ergonomics, Scientific Institute of Veruno, Fondazione Salvatore Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Veruno, Italy; Department of Physical Medicine and Rehabilitation, University of Turin, Turin, Italy; Department of Neurorehabilitation, Scientific Institute of Veruno, Fondazione Salvatore Maugeri, Istituto di Ricovero e Cura a Carattere Scientifico, Veruno, Italy; Department of Surgical Science, University of Turin, Turin, Italy

Does early verbal fluency decline after STN implantation predict long-term cognitive outcome after STN-DBS in Parkinson's disease?

BACKGROUNDS An early and transient verbal fluency (VF) decline and impairment in frontal executive function, suggesting a cognitive microlesion effect may influence the cognitive repercussions related to subthalamic nucleus deep brain stimulation (STN-DBS). METHODS Neuropsychological tests including semantic and phonemic verbal fluency were administered both before surgery (baseline), the third day after surgery (T3), at six months (T180), and at an endpoint multiple years after surgery (Tyears). RESULTS Twenty-four patients (mean age, 63.5 ± 9.5 years; mean disease duration, 12 ± 5.8 years) were included. Both semantic and phonemic VF decreased significantly in the acute post-operative period (44.4 ± 28.2% and 34.3 ± 33.4%, respectively) and remained low at 6 months compared to pre-operative levels (decrease of 3.4 ± 47.8% and 10.8 ± 32.1%) (P < 0.05). Regression analysis showed phonemic VF to be an independent factor of decreased phonemic VF at six months. Age was the only independent predictive factor for incident Parkinsons disease dementia (PDD) (F (4,19)=3.4, P<0.03). CONCLUSION An acute post-operative decline in phonemic VF can be predictive of a long-term phonemic VF deficit. The severity of this cognitive lesion effect does not predict the development of dementia which appears to be disease-related.

Teaching NeuroImages: Ataxia and diabetes insipidus

A 63-year-old woman presented with recent cerebellar ataxia. Diabetes insipidus had been diagnosed 35 years earlier. Brain MRI showed fluid-attenuated inversion recovery hyperintensities involving cerebellar peduncles and pons, with punctiform gadolinium enhancement on T1 sequences (figure, A). Leg X-rays revealed cortical osteosclerosis of both tibias (figure, B). Tibia biopsy revealed bone remodeling associated with bone marrow fibrosis and lymphohistiocytic reaction confirming the diagnosis of Erdheim-Chester disease (ECD).

Chorea in an 83-year-old woman: don't forget Huntington's disease.

An 83-year-old woman presented to the Neurology Department with a 3-year history of progressively uncontrollable movements. Her past medical history included hypertension and non-insulin-dependent diabetes mellitus. She was the second of three children and had no children of her own. There was no family history of abnormal movements or mental disease. Before the onset of the movements, she had never taken antidopaminergic medications. The involuntary abnormal movements had begun insidiously 3 years earlier with lower limb jerks mimicking myoclonus. Because no other neurological abnormalities were found, essential myoclonus was initially diagnosed, and oral diazepam was initiated, leading to mild transient improvement. Over the following months, she noted that the movements gradually worsened and spread to her upper extremities and face. Two years later, she complained of gait instability and needed crutches to walk. She never complained of depression, and close relatives reported no psychiatric symptoms. Physical examination revealed generalized choreic movements involving not only the four extremities, but also the trunk, head, and face. Chorea was present at rest and was exacerbated by stress and emotion. In addition, she experienced jerky intrusions when attempting to perform smooth pursuit eye movements. Neurological examination showed moderate dysarthria and gait instability. Although she did not have memory complaints, specific cognitive evaluation revealed memory impairment and dysexecutive dysfunction (Mini-Mental State Examination score 19/30; Mattis Rating Scale score 119/144) without behavioral disturbance. Standard biological data were unremarkable. Diabetes mellitus was well controlled, and thyroid levels were normal. Brain magnetic resonance imaging (MRI) showed only mild leukoaraiosis and no other abnormalities, in particular, no atrophy of caudate nuclei (Figure 1). Because her regular medication was not known to induce choreic movements, genetic testing was proposed with informed consent to exclude HD. Molecular genetic analysis revealed an expanded allele with 40 CAG repeats, confirming the hypothesis. Tetrabenazine was started, which led to a reduction in intensity of chorea, and the woman was referred for genetic counseling and support group. The usual etiologies of senile chorea include drugs, medications, cerebrovascular disease, genetic and sporadic neurodegenerations, and a range of systemic (hematological, metabolic, and immune) disorders. Nevertheless, studies have revealed that the majority of individuals with senile chorea have HD. HD is a rare autosomal-dominant neurodegenerative disease caused by a CAG expansion in the 5′ region of the HTT gene. The normal range of CAG repeats varies from six to 36. Mutations between 36 and 39 repeats are considered to have less penetrance. Onset usually occurs by the fourth to fifth decade of life, but it can present at any age, with a broad range of 2–85 years. Diagnosis is made based on clinical features and family history and is then confirmed by genetic testing. No complementary examinations aid in diagnosis, even if brain MRI can reveal atrophy of the striatum, especially the caudate nuclei. Although there is no established treatment to delay the onset or forestall the progression of HD, symptomatic treatment of chorea may be beneficial in some individuals, because it may have a favorable effect on motor function, quality of life, and safety. Peculiar clinical characteristics of late-onset HD have been detailed elsewhere. As in our case, most (68%) individuals with late onset of the disease are the first in their family to be diagnosed with HD. In these late-onset cases, disease usually begins with motor problems, and disease duration is somewhat shorter than that reported for the midlife-onset form of the disease. Furthermore, serious falls are a major risk, and global dementia may be associated with coincident Alzheimer’s disease. Finally, death is often related to aging-associated diseases such as cancer and cerebrovascular disease. Because the majority of individuals with “senile” chorea have HD even in the absence of a family history, the case discussed here is a reminder that the diagnosis of HD should be considered whatever the age. This diagnosis has major consequences for genetic counseling.