Maria José Rosas

SANDO: Two novel mutations in POLG1 gene

Sensory ataxia with neuropathy, dysarthria and ophthalmoparesis represent the clinical triad of SANDO, a specific mitochondrial phenotype first reported in 1997 in association with multiple mitochondrial DNA deletions and mutations in POLG1 or more rarely in the C10orf2 (twinkle-helicase) gene. We report a 44-year-old man with SANDO who harboured two novel mutations (P648R/R807C) in the POLG1 gene.

Suicide Attempts after Subthalamic Nucleus Stimulation for Parkinson’s Disease

A higher risk of suicidal attempt after subthalamic nucleus deep brain stimulation (STN-DBS) for Parkinson’s disease (PD) has been consistently reported. We retrospectively analyzed 3 PD patients with suicide attempts after STN-DBS. All patients had normal pre- and immediate postoperative psychopathological and cognitive evaluations, with STN-DBS yielding a good motor benefit. Levodopa medication was markedly reduced. Albeit there was a significant reduction in dopaminergic medication, there was also a considerable time lag to suicide attempt. Impulsive behavior could have played a higher role, going unnoticed in punctual psychopathological examinations. STN-DBS patients need a closer postoperative psychiatric and behavioral follow-up.

Transient disabling dyskinesias: a predictor of good outcome in subthalamic nucleus deep brain stimulation in Parkinson's disease.

We report 5 of 75 (6.6%) patients with Parkinson’s disease (PD) submitted to subthalamic nucleus deep brain stimulation (STN-DBS) who developed transient disabling dyskinesias immediately after surgery. Dyskinesias persisted despite levodopa withdrawal, cessation or reduction of stimulation, and resolved spontaneously in a maximum period of 12 weeks without the need to change stimulation active contact. Compared to the rest of our PD patients submitted to STN-DBS, the dyskinesia group needed a lower levodopa-equivalent daily dosage (LEDD) over the time of follow-up. A microlesion in the STN, probably concealed in cerebral MRI by the electrode-related artifact, could have been involved in the etiopathology of our patients’ symptoms. The presence of transient disabling dyskinesia in PD patients immediately after STN-DBS might be a predictor of good outcome as measured by a decrease in the LEDD needed.

POLG1-related levodopa-responsive parkinsonism.

Parkinsonian features have been described in patients with POLG1 mutations. Notwithstanding, the clinical expression has been revealed heterogeneous and the response to dopaminergic treatment has been document in few cases. We aim to describe the longitudinal clinical features and the treatment response of three unrelated patients with neurodegenerative parkinsonism, preceded by PEO and SANDO syndromes, who harbor POLG1 mutations, including two novel mutations. It was documented a sustained response to levodopa, at 3 and 8 years of follow-up of parkinsonian syndrome, and reduced striatal dopamine uptake. We review the genotypic and phenotypic spectrum of POLG1-related parkinsonism. Our observations stimulate the debate around the role of mitochondrial DNA defects in the pathogenesis of neurodegenerative parkinsonism.

Kinect v2 based system for Parkinson's disease assessment.

Human motion analysis can provide valuable information for supporting the clinical assessment of movement disorders, such as Parkinsons disease (PD). In this contribution, we study the suitability of a Kinect v2 based system for supporting PD assessment in a clinical environment, in comparison to the original Kinect (v1). In this study, 3-D body joint data were acquired from both normal subjects, and PD patients treated with deep brain stimulation (DBS). Then, several gait parameters were extracted from the gathered data. The obtained results show that 96% of the considered parameters are appropriate for distinguishing between non-PD subjects, PD patients with DBS stimulator switched on, and PD patients with stimulator switched off (p-value <; 0.001, Kruskal-Wallis test). These results are markedly better than the ones obtained using Kinect v1, where only 73% of the parameters are considered appropriate (p-value <; 0.001).

Early deep brain stimulation in patients with myoclonus-dystonia syndrome

Myoclonus-dystonia (MD) is a rare movement disorder which is disabling and frequently refractory to medical treatment. Deep brain stimulation (DBS) of the globus pallidus interna (GPi) has been used to treat some patients. Although there is significant motor improvement with DBS, the impact on disability and on quality of life has been infrequently reported. Also, the benefit of the procedure is not established in patients without ε-sarcoglycan gene (SGCE) mutations. We present two patients with severe MD treated with GPi-DBS, one of the patients without a SGCE mutation. Motor improvements (rest/action/total subscores of the Unified Myoclonus Rating Scale and movement subscore of the Burke-Fahn-Marsden Dystonia Rating Scale [BFMRS]) and disability (BFMRS disability subscore) were carefully evaluated preoperatively and at 6 and 12months after surgery. Quality of life (addressed using the Portuguese version of the Medical Outcomes Study 36-item Short-Form General Health Survey, version 2.0 [SF-36v2]) was tested preoperatively and 12months after DBS. At 12-month follow-up, myoclonus improved 78.6% in Patient 1 and 80.7% in Patient 2, while dystonia improved 37% and 86.7%, respectively. Improvements in disability ranged from 71.4% to 75%. With regard to quality of life, all parameters addressed by the SF-36v2 improved or stabilized in both patients. No major adverse effects were noticed. Improvements in motor symptoms are consistent with reports in the literature and were obtained regardless of the identification of a SGCE gene mutation. There were also significant benefits on disability and quality of life. DBS should be considered for MD.

Twiddler (or Not) Syndrome: Questioning etiology for an uncommon form of hardware malfunction in deep brain stimulation.

Background: Hardware failure or malfunction after deep brain stimulation is an infrequent but costly occurrence with currently available systems. Case Description: The authors present the case of a 65-year-old female patient with predominantly tremoric Parkinsons disease who, 4 months after bilateral subthalamic nucleus stimulation with very good clinical results, began to display signs of recurrent disease and an increasingly smaller response to stimulation. Radiological studies, changes in electrode impedance and surgical findings and results established the diagnosis of Twiddler syndrome. Close patient follow-up, lack of a psychiatric history and physical examination findings were, however, contrary to the previously described causative mechanism. Conclusion: The clinical and radiological setup of Twiddler syndrome must be readily recognized. Its causative mechanism should remain under discussion, and intraoperative technical details may help to explain its occurrence.

Role of 99mTc-Sulesomab Immunoscintigraphy in the Management of Infection following Deep Brain Stimulation Surgery

Infection constitutes a serious adverse event in patients submitted to deep brain stimulation, often leading to removal of the device. We set to evaluate the potential role of immunoscintigraphy with 99mTc-labelled antigranulocyte antibody fragments (99mTc-sulesomab) in the management of infection following DBS. 99mTc-sulesomab immunoscintigraphy seems to correlate well with the presence and extent of infection, thus contributing to differentiate between patients who should remove the hardware entirely at presentation and those who could undergo a more conservative approach. Also, 99mTc-sulesomab immunoscintigraphy has a role in determining the most appropriate timing for reimplantation. Finally, we propose an algorithm for the management of infection following DBS surgery, based on the results of the 99mTc-sulesomab immunoscintigraphy.

Deep Brain Stimulation of the Subthalamic Nucleus for Parkinson's Disease in a Patient with HIV Infection: Dual Clinical Benefit.

As a result of the efficacy of highly active antiretroviral therapy (HAART), patients with human immunodeficiency virus (HIV) can survive longer and are thus naturally prone to ageing-related degenerative disorders such as Parkinson’s disease (PD). Managing PD and HIV in the same patient may be challenging, as HAART and levodopa interact and may cause intolerable side effects. Concerns about the increased risk of hardware infection in immunocompromised patients submitted to deep brain stimulation of the subthalamic nucleus (STN-DBS) still persist. We report a PD patient with HIV infection who suffered peak-dose dyskinesias and intolerable gastrointestinal side effects while on HAART, prompting its suspension. STN-DBS allowed complete postoperative levodopa withdrawal and HAART restart, without infectious complications after 12 months of follow-up. STN-DBS seems to be a safe procedure in selected patients with both medically refractory PD and HIV infection, and may result in clinical optimization of both conditions.

Chronobiology of Cerebral Vein and Dural Sinus Thrombosis

Chronobiology of Cerebral Vein and Dural Sinus Thrombosis José M. Ferro a, Gabriela C. Lopes c, Maria José Rosas d, Carolina Araújo b, Isabel Henriques e for the VENOPORT investigators Departments of Neurology, Hospitals of a Santa Maria and bSão José, Lisbon, Departments of Neurology, Hospitals of cSanto António and dSão João, Porto, and e Department of Neurology, Hospital of Espı́rito Santo, Évora, Portugal