Fátima Carrillo

Distinguishing SWEDDs Patients with Asymmetric Resting Tremor from Parkinson's Disease: A Clinical and Electrophysiological Study

Approximately 10% of patients diagnosed clinically with early Parkinsons disease (PD) have normal dopaminergic functional imaging (Scans Without Evidence of Dopaminergic Deficit [SWEDDs]). An important subgroup of SWEDDs are those with asymmetric rest tremor resembling parkinsonian tremor. Clinical and pathophysiological features which could help to distinguish SWEDDs from PD have not been explored. We therefore studied clinical details including non‐motor symptoms in 25 tremulous SWEDDs patients in comparison to 25 tremor‐dominant PD patients. Blinded video rating was used to compare examination findings. Electrophysiological tremor parameters and also response to a cortical plasticity protocol using paired associative stimulation (PAS) was studied in 9 patients with SWEDDs, 9 with tremor‐dominant PD (with abnormal dopamine transporter single photon emission computed tomography findings), 8 with segmental dystonia, and 8 with essential tremor (ET). Despite clinical overlap, lack of true bradykinesia, presence of dystonia, and head tremor favored a diagnosis of SWEDDs, whereas re‐emergent tremor, true fatiguing or decrement, good response to dopaminergic drugs, and presence of non‐motor symptoms favored PD. A single tremor parameter could not differentiate between groups, but the combination of re‐emergent tremor and highest tremor amplitude at rest was characteristic of PD tremor. SWEDDs and segmental dystonia patients exhibited an abnormal exaggerated response to the PAS protocol, in contrast to a subnormal response in PD and a normal response in ET. We conclude that despite clinical overlap, there are features that can help to distinguish between PD and SWEDDs which may be useful in clinical practice. The underlying pathophysiology of SWEDDs differs from PD but has similarities with primary dystonia.

Olfaction in patients with suspected Parkinsonism and scans without evidence of dopaminergic deficit (SWEDDs)

Background: Positron emission tomography and single photon emission computed tomography scanning have 87–94% sensitivity and 80–100% specificity to differentiate patients with Parkinson’s disease (PD) from control subjects and patients with essential (ET) or atypical tremor. More than 10% of patients diagnosed as early PD can have scans without evidence of dopaminergic deficiency (SWEDDs). This study investigated whether smell tests can help identify possible cases with SWEDDs. Methods: The 40 item University of Pennsylvania Smell Test (UPSIT) was used to evaluate the sense of smell in 21 SWEDDs patients. Twenty-six ET patients, 16 patients with a diagnosis of idiopathic adult onset dystonia (D), 191 non-demented PD patients and 136 control subjects were also tested. Multiple regression analyses were used to compare the mean UPSIT score in the SWEDDs group with the other four groups (ET, D, PD and controls) after adjusting for the effects of relevant covariates. Results: The mean UPSIT score for the SWEDDs group was greater than in the PD group (p<0.001) and not different from the mean UPSIT in the control (p = 0.7), ET (p = 0.4) or D (p = 0.9) groups. Smell tests indicated a high probability of PD in only 23.8% of SWEDDs as opposed to 85.3% of PD patients. Conclusions: In a patient with suspected PD, a high PD probability on smell testing favours the diagnosis of PD, and a low PD probability strengthens the indication for dopamine transporter imaging.

Effects of Two Weeks of Cerebellar Theta Burst Stimulation in Cervical Dystonia Patients

Dystonia is generally regarded as a disorder of the basal ganglia and their efferent connections to the thalamus and brainstem, but an important role of cerebellar-thalamo-cortical (CTC) circuits in the pathophysiology of dystonia has been invoked. Here in a sham controlled trial, we tested the effects of two-weeks of cerebellar continuous theta burst stimulation (cTBS) in a sample of cervical dystonia (CD) patients. Clinical evaluations were performed by administering the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) and the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS). We used TMS to measure the inhibitory connectivity between the cerebellum and the contralateral motor cortex (cerebellar brain inhibition [CBI]), and the excitability of the contralateral primary motor cortex assessing intracortical inhibition (SICI), intracortical facilitation (ICF) and cortical silent period (CSP). Paired associative stimulation (PAS) was tested to evaluate the level and the topographical specificity of cortical plasticity, which is abnormally enhanced and non-focal in CD patients. Two weeks of cerebellar stimulation resulted in a small but significant clinical improvement as measured by the TWSTRS of approximately 15%. Cerebellar stimulation modified the CBI circuits and reduced the heterotopic PAS potentiation, leading to a normal pattern of topographic specific induced plasticity. These data provide novel evidence CTC circuits could be a potential target to partially control some dystonic symptoms in patients with cervical dystonia.

Clinical features and 123I-FP-CIT SPECT imaging in vascular parkinsonism and Parkinson's disease

Objectives To analyse the differences in the clinical features and characteristics of 123I-labelled 2β-carbomethoxy-3β-(4-iodophenyl)-N-(3-fluoropropyl) nortropane (123I-FP-CIT) single photon emission CT (SPECT) imaging among patients with vascular parkinsonism (VP) and Parkinsons disease (PD). Methods We performed a case–control study to compare clinical features and qualitative and semi-quantitative analyses of 123I-FP-CIT SPECT images between 106 patients with VP and 280 patients with PD. A case series study was used to search for clinical features related to SPECT or neuroimaging findings among patients with VP. Results Patients with VP had a higher age at symptom onset and lower disease duration than patients with PD. The most frequent symptom at onset was gait disorder in VP and tremor in PD. Gait disorder, postural instability and falls were more frequent in VP. Rest and mixed tremor were more prevalent in PD. Of the patients who received levodopa treatment in the VP group, only about half had a good response. Qualitatively 123I-FP-CIT SPECT images were normal in 32.5% of patients with VP and abnormal in all patients with PD. The use of different visual score patterns showed higher ability to differentiate VP from PD. Semi-quantitative analysis showed significantly higher uptake in the striatum, caudate and putamen in VP. The asymmetry index was higher in patients with PD. Among patients with VP, falls were the only clinical feature that demonstrated a correlation with the SPECT visual pattern. Conclusion Our data contribute to the confirmation that VP and PD are two different clinical entities. Neurological signs, response to treatment and qualitative and semi-quantitative 123I-FP-CIT SPECT analyses may help to make the diagnosis.

Study of cerebello-thalamocortical pathway by transcranial magnetic stimulation in Parkinson's disease.

BACKGROUND Although functional changes in the activation of the cerebellum in Parkinsons disease (PD) patients have been consistently described, it is still debated whether such altered cerebellar activation is a natural consequence of PD pathophysiology or rather it involves compensatory mechanisms. OBJECTIVE/HYPOTHESIS We used different forms of cerebellar transcranial magnetic stimulation to evaluate the hypothesis that altered cerebello-cortical interactions can be observed in PD patients and to evaluate the role of dopaminergic treatment. METHODS We studied the effects of a single cerebellar magnetic pulse over the excitability of the contralateral primary motor cortex tested with motor-evoked potentials (MEPs) (cerebellar-brain inhibition-CBI) in a group of 16 PD patients with (ON) and without dopaminergic treatment (OFF), and in 16 age-matched healthy controls. Moreover, we also tested the effects of cerebellar continuous theta-burst stimulation (cTBS) on MEP amplitude, short intracortical inhibition (SICI) and short intracortical facilitation (SICF) tested in the contralateral M1 in 13 PD patients in ON and OFF and in 16 age-matched healthy controls. RESULTS CBI was evident in controls but not in PD patients, even when tested in both ON and OFF conditions. Similarly, cerebellar cTBS reduced MEP amplitude and SICI in controls but not in PD patients under any condition. CONCLUSION(S) These results demonstrate that PD patients have deficient short-latency and long-lasting cerebellar-thalamocortical inhibitory interactions that cannot be promptly restored by standard dopaminergic medication.

Genetic Variability Related to Serum Uric Acid Concentration and Risk of Parkinson's Disease

Low serum uric acid (UA) levels have been associated with increased Parkinsons disease (PD) risk and accelerated disease progression. We analyzed the effect of polymorphisms in 9 genes influencing serum UA concentration on the risk of PD.

Brain-derived neurotrophic factor G196A polymorphism and clinical features in Parkinson's disease.

Gao L, Díaz‐Corrales FJ, Carrillo F, Díaz‐Martín J, Caceres‐Redondo MT, Carballo M, Palomino A, López‐Barneo J, Mir P. Brain‐derived neurotrophic factor G196A polymorphism and clinical features in Parkinson’s disease.
Acta Neurol Scand: 2010: 122: 41–45.
© 2010 The Authors Journal compilation

Prominent Oromandibular Dystonia and Pharyngeal Telangiectasia in Atypical Ataxia Telangiectasia

Ataxia telangiectasia (A-T) typically presents with early-onset progressive cerebellar ataxia, oculomotor apraxia and later, oculo-cutaneous telangiectasia. Extrapyramidal symptoms, apart from chorea, are rare. In this paper, we report a case of A-T with an atypically mild and slowly progressive disease course. Although by history there was mild gait clumsiness in early childhood, the leading problem was that of dystonia with onset at age 15, in the absence of gross gait imbalance or ocular motor apraxia. Dystonia was generalized and with prominent oromandibular involvement. Unusually, a leash of telangiectasia was present on the posterior pharyngeal wall, while other features frequently associated with A-T were absent.

Prevalence and clinical features of LRRK2 mutations in patients with Parkinson’s disease in southern Spain

Background and purpose: Mutations in leucine‐rich repeat kinase 2 (LRRK2) gene are associated with both familial and idiopathic Parkinson’s disease (PD), whereas mutations in PARK2 (PARKIN) gene result in early onset recessive PD. Here, the objectives were to determine the frequency of LRRK2 G2019S and R1441G mutations in a PD population from southern Spain; to search for LRRK2 mutations in familial PD cases and to study the effect of PARKIN mutations on clinical features of LRRK2‐associated; PD.

Low serum uric acid concentration in Parkinson's disease in southern Spain

Uric acid (UA) is thought to have an antioxidant effect on the central nervous system and may also prevent cerebral damage induced by oxidative stress. Our study aimed to investigate whether patients with Parkinsons disease (PD) had lower serum UA concentrations than controls and whether UA concentration was related to clinical parameters of the disease.