Levodopa-responsive Holmes' Tremor Caused by a Single Inflammatory Demyelinating Lesion

<p><strong>Background</strong>: Holmes&rsquo; tremor is characterized by a combination of rest, postural, and kinetic tremor that is presumably caused by interruption of cerebello-thalamo-cortical and nigrostriatal pathways. Medical treatment remains unsatisfactory.</p><p><strong> Case Report</strong>: A 16-year-old girl presented with Holmes&rsquo; tremor caused by a transient midbrain abnormality on magnetic resonance imaging (MRI). To explore the discrepancy between persistent tremor and resolved MRI changes, we performed dopamine transporter single-photon emission computed tomography (DaT-SPECT) with a 123I-ioflupane that revealed nearly absent DaT binding in the right striatum. Levodopa dramatically improved the tremor.</p><p><strong> Discussion</strong>: This is only the second report of a transient midbrain MRI abnormality disrupting nigrostriatal pathways. The case highlights the sometimes limited sensitivity of morphologic imaging for identifying the functional consequences of tissue damage and confirms that DaT imaging may serve as a predictor for levodopa responsiveness in Holmes&rsquo; tremor.</p

Quantitative Susceptibility Mapping in Parkinson's Disease.

BACKGROUND:Quantitative susceptibility mapping (QSM) and R2* relaxation rate mapping have demonstrated increased iron deposition in the substantia nigra of patients with idiopathic Parkinson's disease (PD). However, the findings in other subcortical deep gray matter nuclei are converse and the sensitivity of QSM and R2* for morphological changes and their relation to clinical measures of disease severity has so far been investigated only sparsely. METHODS:The local ethics committee approved this study and all subjects gave written informed consent. 66 patients with idiopathic Parkinson's disease and 58 control subjects underwent quantitative MRI at 3T. Susceptibility and R2* maps were reconstructed from a spoiled multi-echo 3D gradient echo sequence. Mean susceptibilities and R2* rates were measured in subcortical deep gray matter nuclei and compared between patients with PD and controls as well as related to clinical variables. RESULTS:Compared to control subjects, patients with PD had increased R2* values in the substantia nigra. QSM also showed higher susceptibilities in patients with PD in substantia nigra, in the nucleus ruber, thalamus, and globus pallidus. Magnetic susceptibility of several of these structures was correlated with the levodopa-equivalent daily dose (LEDD) and clinical markers of motor and non-motor disease severity (total MDS-UPDRS, MDS-UPDRS-I and II). Disease severity as assessed by the Hoehn & Yahr scale was correlated with magnetic susceptibility in the substantia nigra. CONCLUSION:The established finding of higher R2* rates in the substantia nigra was extended by QSM showing superior sensitivity for PD-related tissue changes in nigrostriatal dopaminergic pathways. QSM additionally reflected the levodopa-dosage and disease severity. These results suggest a more widespread pathologic involvement and QSM as a novel means for its investigation, more sensitive than current MRI techniques

Validation of "laboratory-supported" criteria for functional (psychogenic) tremor

BACKGROUND: In a small group of patients, we have previously shown that a combination of electrophysiological tests was able to distinguish functional (psychogenic) tremor and organic tremor with excellent sensitivity and specificity. OBJECTIVES: This study aims to validate an electrophysiological test battery as a tool to diagnose patients with functional tremor with a "laboratory-supported" level of certainty. METHODS: For this prospective data collection study, we recruited 38 new patients with functional tremor (mean age 37.9 ± 24.5 years; mean disease duration 5.9 ± 9.0 years) and 73 new patients with organic tremor (mean age 55.4 ± 25.4 years; mean disease duration 15.8 ± 17.7 years). Tremor was recorded at rest, posture (with and without loading), action, while performing tapping tasks (1, 3, and 5 Hz), and while performing ballistic movements with the less-affected hand. Electrophysiological tests were performed by raters blinded to the clinical diagnosis. We calculated a sum score for all performed tests (maximum of 10 points) and used a previously suggested cut-off score of 3 points for a diagnosis of laboratory-supported functional tremor. RESULTS: We demonstrated good interrater reliability and test-retest reliability. Patients with functional tremor had a higher average score on the test battery when compared with patients with organic tremor (3.6 ± 1.4 points vs 1.0 ± 0.8 points; P < .001), and the predefined cut-off score for laboratory-supported functional tremor yielded a test sensitivity of 89.5% and a specificity of 95.9%. CONCLUSION: We now propose this test battery as the basis of laboratory-supported criteria for the diagnosis of functional tremor, and we encourage its use in clinical and research practice. © 2016 International Parkinson and Movement Disorder Society

Regional magnetic susceptibility and R2* values.

<p>Regional magnetic susceptibility and R2* values.</p

Univariate correlations of R2* and magnetic susceptibility with clinical parameters for patients with PD.

<p>Univariate correlations of R2* and magnetic susceptibility with clinical parameters for patients with PD.</p

Regional mean susceptibilities and R2* (±standard deviation).

<p>Asterisks denote significant differences between controls and patients with Parkinson’s disease (*p<0.05; **p<0.01; ***p< = 0.001).</p

Clinical and demographic data of the study cohort.

<p>Clinical and demographic data of the study cohort.</p

Univariate correlations of R2* and magnetic susceptibility for patients with shorter and longer disease duration dichotomized by median disease duration (3.4 years).

<p>Univariate correlations of R2* and magnetic susceptibility for patients with shorter and longer disease duration dichotomized by median disease duration (3.4 years).</p

Representative T1-weighted MP-RAGE image (left) with color overlay of segmented deep gray matter structures, R2* relaxation rate constant map (center) and quantitative susceptibility map (right) of a 62-years patient with PD (MDS-UPDRS 46; Hoehn & Yahr 2).

<p>High R2* rates and paramagnetic susceptibilities are found in the basal ganglia. Note the improved gray-white matter contrast on the QSM map compared to the R2* map.</p