Miguel Gago

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.

Deep brain stimulation does not change neurovascular coupling in non-motor visual cortex: An autonomic and visual evoked blood flow velocity response study

BACKGROUND AND PURPOSE In Parkinsons disease (PD) subthalamic nucleus deep brain stimulation (STN-DBS) improves motor function. Also an effect on the neurovascular coupling in motor cortex was reported due to a parallel activation of a subthalamic vasodilator area (SVA). To address this issue further we analysed neurovascular coupling in a non-motor area. METHODS Twenty PD patients selected for bilateral STN-DBS were investigated with functional transcranial Doppler (f-TCD) before and after surgery. Hemodynamic responses to visual stimulation were registered in left posterior cerebral artery (PCA) and analysed with a control-system approach (parameters gain, rate time, attenuation and natural frequency). To exclude autonomic effects of STN-DBS, we also addressed spectrum analysis of heart rate and of systolic arterial blood pressure variability, and baroreceptor gain. Findings in the PD group were compared with healthy age-matched controls. RESULTS PD patients showed no neurovascular coupling changes in PCA territory, compared to controls, and STN-DBS changed neither blood flow regulatory parameters nor autonomic function. CONCLUSIONS Improvement of vasoregulation in some motor cortical areas after STN-DBS might be related to an improved neuronal functional rather than indicating an effect on the neurovascular coupling or autonomic function.

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.

Compensatory postural adjustments in Parkinson's disease assessed via a virtual reality environment.

Postural control is a complex dynamic mechanism, which integrates information from visual, vestibular and somatosensory systems. Idiopathic Parkinsons disease (IPD) patients are unable to produce appropriate reflexive responses to changing environmental conditions. Still, it is controversial what is due to voluntary or involuntary postural control, even less what is the effect of levodopa. We aimed to evaluate compensatory postural adjustments (CPA), with kinematic and time-frequency analyzes, and further understand the role of dopaminergic medication on these processes. 19 healthy subjects (Controls) and 15 idiopathic Parkinsons disease (IPD) patients in the OFF and ON medication states, wearing IMUs, were submitted to a virtual reality scenario with visual downward displacements on a staircase. We also hypothesized if CPA would involve mechanisms occurring in distinct time scales. We subsequently analyzed postural adjustments on two frequency bands: low components between 0.3 and 1.5 Hz (LB), and high components between 1.5 and 3.5 Hz (HB). Vertical acceleration demonstrated a greater power for discriminating IPD patients from healthy subjects. Visual perturbation significantly increased the power of the HB in all groups, being particularly more evident in the OFF state. Levodopa significantly increased their basal power taking place on the LB. However, controls and IPD patients in the ON state revealed a similar trend of the control mechanism. Results indicate an improvement in muscular stiffness provided by levodopa. They also suggest the role of different compensatory postural adjustment patterns, with LB being related to inertial properties of the oscillating mass and HB representing reactions to the ongoing visual input-changing scenario.

Role of the Visual and Auditory Systems in Postural Stability in Alzheimer's Disease.

BACKGROUND Postural stability requires the integration of multisensory input information and translation into appropriate motor responses. Surprisingly, few previous studies have addressed the role of auditory input on postural stability in healthy subjects, and none has investigated this in Alzheimers disease (AD). OBJECTIVE To assess the influence of the visual and auditory systems on postural stability in patients with AD and healthy subjects. METHODS Twenty-four patients with AD and healthy age-matched subjects were examined by kinematic postural analysis (inertia measurement units placed at the center of mass of the body) under four different conditions: stance with eyes open and eyes closed, with and without suppression of background noise (using ear defenders). The effects of visual and auditory influences were analyzed independently and in conjunction. RESULTS In both groups, visual suppression had a negative impact on postural stability, while suppression of background noise, non-specifically and without spatial cues, significantly benefited postural stability. We also observed that in both groups, the positive effect of background noise suppression was insufficient to compensate for the negative effect of visual suppression, to which the patients were significantly more vulnerable. CONCLUSIONS Audition, albeit less significant than vision, also plays a role in the multi-sensorial dynamic control of postural stability by the central nervous system. In everyday life, audition is likely to be a relevant factor in postural stability. This is especially relevant in AD in which, even when the peripheral sensory system is intact, the central processing is impaired and sensory dependence is re-weighted.

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.

Application of Machine Learning in Postural Control Kinematics for the Diagnosis of Alzheimer’s Disease

The use of wearable devices to study gait and postural control is a growing field on neurodegenerative disorders such as Alzheimers disease (AD). In this paper, we investigate if machine-learning classifiers offer the discriminative power for the diagnosis of AD based on postural control kinematics. We compared Support Vector Machines (SVMs), Multiple Layer Perceptrons (MLPs), Radial Basis Function Neural Networks (RBNs), and Deep Belief Networks (DBNs) on 72 participants (36 AD patients and 36 healthy subjects) exposed to seven increasingly difficult postural tasks. The decisional space was composed of 18 kinematic variables (adjusted for age, education, height, and weight), with or without neuropsychological evaluation (Montreal cognitive assessment (MoCA) score), top ranked in an error incremental analysis. Classification results were based on threefold cross validation of 50 independent and randomized runs sets: training (50%), test (40%), and validation (10%). Having a decisional space relying solely on postural kinematics, accuracy of AD diagnosis ranged from 71.7 to 86.1%. Adding the MoCA variable, the accuracy ranged between 91 and 96.6%. MLP classifier achieved top performance in both decisional spaces. Having comprehended the interdynamic interaction between postural stability and cognitive performance, our results endorse machine-learning models as a useful tool for computer-aided diagnosis of AD based on postural control kinematics.