Joohi Jimenez Shahed

GPi deep brain stimulation for Tourette syndrome improves tics and psychiatric comorbidities

Tourette syndrome (TS) is characterized by phonic and motor tics and psychiatric comorbidities including attention-deficit (± hyperactivity) disorder (AD/HD), obsessive-compulsive behavior (OCB), anxiety, depression, and others.1 The efficacy and safety of deep brain stimulation (DBS) in movement disorders are established, and their applicability to neuropsychiatric conditions is expanding. We describe the results of bilateral DBS of the globus pallidus interna (GPi) in a 16-year-old boy with severe, medication-refractory TS. This left-handed boy presented at age 15 years for evaluation of escalating TS. Tics began at age 3, OCB by age 5, and AD/HD, coprolalia, copropraxia, and loud screaming by age 7. Haloperidol, pimozide, fluphenazine, benzodiazepines, guanfacine, selective serotonin reuptake inhibitors, tetrabenazine, and botulinum toxin injections (vocal cords) failed to relieve symptoms, including touching and grabbing others, self-gagging until emesis, eye poking, facial self-excoriations, self-hitting, and screaming until hoarse. Anxiety, depression, hyperactivity, and impulsivity were notable, while inattention and opposition were less problematic. His marked academic and social impairment prompted consideration of DBS surgery. Neuropsychological evaluation assessed suitability …

Malignant Tourette syndrome

The aim of this work was to draw attention to potentially life‐threatening symptoms associated with Tourette syndrome (TS) and to explore their relationship to TS comorbidities. Medical records of all patients with TS evaluated at our Movement Disorders Clinic between July 2003 and July 2006 were reviewed. Data on patients with malignant TS, defined as ≥2 emergency room (ER) visits or ≥1 hospitalizations for TS symptoms or its associated behavioral comorbidities, were entered into a dataset and analyzed. Five illustrative cases are described. Of 333 TS patients evaluated during the 3‐year period, 17 (5.1%) met the criteria for malignant TS. Hospital admission or ER visits were for tic‐related injuries, self‐injurious behavior (SIB), uncontrollable violence and temper, and suicidal ideation/attempts. Compared with patients with nonmalignant TS, those with malignant TS were significantly more likely to have a personal history of obsessive compulsive behavior/disorder (OCB/OCD), complex phonic tics, coprolalia, copropraxia, SIB, mood disorder, suicidal ideation, and poor response to medications. Although TS is rarely a disabling disorder, about 5% of patients referred to a specialty clinic have life‐threatening symptoms. Malignant TS is associated with greater severity of motor symptoms and the presence of ≥2 behavioral comorbidities. OCD/OCB in particular may play a central role in malignant TS; obsessive compulsive qualities were associated with life‐threatening tics, SIB, and suicidal ideation. Malignant TS is more refractory to medical treatment than nonmalignant TS.

Globus pallidus deep brain stimulation in dystonia

Globus pallidus deep brain stimulation (GPi‐DBS) is a useful alternative in the treatment of dystonia. Patients selected for GPi‐DBS were prospectively rated with the Unified Dystonia Rating Scale (UDRS). Also, “blinded” videotape assessments were performed. Eleven patients were identified. Compared with pre‐DBS scores, there were improvements in mean total UDRS score (15.3%) and in the following subscores: neck (18.18%), trunk (32.9%), arm(17.9%), and leg (19.9%). One patient developed a skin infection and erosion requiring surgical debridement. GPi‐DBS is a safe and effective treatment for generalized dystonia in patients who remained impaired, despite optimal medical therapy.

The effects of subthalamic nucleus deep brain stimulation on parkinsonian tremor

Deep brain stimulation (DBS) of the ventral intermediate (Vim) nucleus of the thalamus has been the target of choice for patients with disabling essential tremor or medication refractory parkinsonian tremor. Recently there is evidence that the subthalamic nucleus (STN) should be the targets for patients with tremor associated with Parkinsons disease (PD). To assess the effects of STN DBS on parkinsonian tremor, eight consecutive patients with PD and disabling tremor were videotaped using a standardized tremor protocol. Evaluations were performed at least 12 h after last dose of medication with the DBS turned off followed by optimal DBS on state. A rater blinded to DBS status evaluated randomized video segments with the tremor components of the Unified Parkinson Disease Rating Scale (UPDRS) and Tremor Rating Scale (TRS). Compared with DBS off state there were significant improvements in mean UPDRS tremor score 79.4% (p=0.008), total TRS score 69.9% (p=0.008) and upper extremity 92.5% (p=0.008) TRS subscore. Functional improvement was noted with pouring liquids. Our findings provide support that STN DBS is an effective treatment of tremor associated with PD.

Re-emergence of childhood stuttering in Parkinson's disease: a hypothesis.

To characterize speech patterns in patients with Parkinsons disease (PD) who have a history of childhood stuttering.

Motor symptoms in Parkinson's disease

Publisher Summary This chapter reviews the pathophysiological mechanisms and the clinical features of motor manifestations of Parkinsons disease (PD). The most typical and easily recognized symptom of PD is unilateral, 4–6 Hz, rest tremor. This is differentiated from the typical 5–8 Hz postural tremor of essential tremor (ET), enhanced physiologic tremor (8–12 Hz), and cerebellar outflow tremor (2–5 Hz). The rest tremor characteristically disappears with action (a feature differentiating it from ET) and during sleep. Stimulation of the subthalamic nucleus (STN), which is typically hyperactive in PD, can also normalize the amplitude and frequency of PD tremor towards physiologic ranges. In PD, the rigidity is usually accompanied by a “cogwheel” phenomenon, probably a manifestation of underlying tremor. Rigidity often increases with reinforcing maneuvers such as voluntary movements of the contralateral limb. This examination technique can greatly assist in the diagnosis of early PD, as the rigidity is ipsilateral to the rest tremor, if present.

Mutation analysis of the parkin and PINK1 genes in American Caucasian early-onset Parkinson disease families

Mutations in the parkin gene and the PTEN-induced putative kinase 1 gene (PINK1) have been identified as the most common causes of autosomal recessive early-onset Parkinson disease (EOPD). To investigate the presence of the parkin and PINK1 gene mutation(s) and to explore genotype-phenotype correlations in American Caucasian families with EOPD from North American, we screened these two genes in probands of six families by direct sequencing, semi-quantitative PCR and RT-PCR. No PINK1 gene mutation was found in any of the probands, but compound heterozygous mutations (EX 3 del and EX 3_4 del) in the parkin gene were identified in one family. Extended analysis of the parkin-positive family showed the phenotype of patients was that of classic autosomal recessive EOPD, characterized by early age at onset, slow progression, beneficial response to levodopa, and levodopa-related motor complications. Three heterozygous mutation carriers (EX 3 del or EX 3_4 del) were free of any neurological symptoms. None of 62 healthy controls harbored EX 3 del or EX 3_4 del mutation. Our data suggest that compound heterozygous mutations (EX 3 and EX 3_4 del) in the parkin gene were the cause of EOPD in one of six Caucasian families; heterozygous EX 3 del and heterozygous EX 3_4 del forms were insufficient to cause this disorder, consistent with a loss-of-function mechanism of the parkin mutations. The results may provide new insights into the cause and diagnosis of PD and have implications for genetic counseling.