Ling-Ling Chan

Case-control study of diffusion tensor imaging in Parkinson’s disease

Background: Preliminary work has shown that diffusion tensor MRI (DTI) may contribute to the diagnosis of Parkinson’s disease (PD). Objectives: We conducted a large, prospective, case control study to determine: (1) if fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in the basal ganglia and substantia nigra are different between patients with PD and healthy controls; and (2) the predictive value of these parameters and their clinical utility. Methods: DTI imaging was carried out in patients with PD and controls. FA and ADC values were obtained from various brain structures on the DTI scan using the diffusion tensor taskcard. The structures studied were: caudate, putamen, globus pallidus, thalamus and substantia nigra. Results: 151 subjects (73 PD patients, 41 men, 32 women; mean age 63.6 years) and 78 age and sex matched control subjects were studied. The FA value of the substantia nigra in patients with PD was lower compared with controls (0.403 vs 0.415; p = 0.001). However, no significant differences were demonstrated for FA or ADC values of other structures. Multiple regression analysis revealed that the clinical severity of PD correlated inversely with the FA value in the substantia nigra in patients with PD (regression coefficient −0.019). No single FA value had both a high positive and negative predictive power for PD. Conclusions: We demonstrated in a large, prospective, case control study that the FA value in the substantia nigra on DTI was lower in PD compared with healthy controls, and correlated inversely with the clinical severity of PD. Further longitudinal studies would be helpful to assess the clinical utility of serial FA measurements of the substantia nigra in objective quantification of disease progression and monitoring of the therapeutic response.

Fragile X premutation alleles in SCA, ET, and parkinsonism in an Asian cohort

Among 367 subjects, the authors analyzed 167 patients with essential tremor, sporadic progressive cerebellar ataxia, multiple-system atrophy, and atypical parkinsonism and 200 healthy control subjects for FMR1 premutation alleles. None of the subjects carried alleles within the premutation range. These findings suggest that in the absence of other supportive clinical or imaging features, the cost-effectiveness of routine fragile X tremor/ataxia syndrome screening in this Asian cohort with movement disorders was low.

Is hypertension associated with hemifacial spasm

Hemifacial spasm (HFS) is characterized by intermittent twitching of the muscles innervated by the ipsilateral facial nerve.1 Reports of normalization of blood pressure after vascular decompression in hypertensive patients suggest an association of hypertension with brainstem compression.2 A recent multicenter case–control study demonstrated a significantly higher prevalence of hypertension in white patients with HFS.3 The cause and effect of hypertension in HFS might have an impact on the management of HFS. Using case–control methodology, we examined the association of hypertension and HFS among HFS patients in our population and investigated differences in neurovascular contact (NVC) of the root exit zone (REZ) of the seventh cranial nerve in HFS patients with and without hypertension using high-resolution MRI/MR angiography (MRA). Methods. Consecutive HFS patients (117) from the movement disorder clinic and controls (245) without HFS seen in the general outpatient clinic for conditions unrelated to hypertension were included in the study. For every HFS patient, we selected two controls of similar age, sex, ethnicity, and body mass index (BMI). A history of hypertension was not an exclusion criterion. All HFS patients were offered brain MRI/MRA as part of the evaluation. We defined hypertension by World Health Organization classification criteria,4 which we also used in our recent National Health Survey (http//www.moh.gov.sg): systolic pressure 140 mm Hg or diastolic pressure 90 mm Hg, or both. Blood pressure was measured using standardized methods3-5 over two to three visits for a period of months as recommended for the diagnosis of hypertension. The imaging comprised three-dimensional time-offlight MRA (TR35, TE6, FA20, 1 nex,192 512 matrix, 1.0-mm partitions) and constructive interference at steady-state sequences (TR12, TE6, FA70, 2 nex, 230 512 matrix, 0.7-mm partitions). A neuroradiologist blinded to the side of HFS interpreted the images. NVC of the seventh cranial nerve was defined as the presence of vascular contact, compression of its REZ, or both. The following data of HFS patients and controls were analyzed: age, sex, duration of HFS, side of HFS, duration of hypertension, associated medical conditions, and MRI/MRA findings. The history of the duration of hemifacial spasm and a history of hypertension were obtained from the patients and corroborated by family members or physicians. Results. The demographics of the study subjects are shown in the table. The mean duration of HFS was 3.9 3.7 (standard deviation [SD]) years (range 0.1 to 20). The mean duration of hypertension in HFS patients and controls was 7.1 8.3 (SD) years (range 0.1 to 30) and 7.2 6.5 (SD) years (range 0.5 to 40). There was no significant difference between the prevalence of hypertension in HFS and controls (see the table). We used multivariate logistic regression analysis with step-wise variable selection for the following variables for both patients and controls: hypertension, diabetes mellitus, renal impairment, ischemic heart disease, cerebrovascular accident, smoking, and alcohol. We did not find significant confounding variables for the association of hypertension with HFS. MRI/MRA was performed in 96 (82.0%) of the 117 HFS patients. NVC of seventh cranial nerve on the side of HFS was found in 90 (93.8%) of patients who underwent MRI/MRA examination. Fourteen of them (14.6%) had NVC bilaterally. The most common offending vessel was the anterior inferior cerebellar artery. The actual vessel could not be identified in 2 of 96 (2.1%). NVC of the seventh cranial nerve was found in 39 of 41 (95.1%) and 51 of 55 (92.7%) in hypertensive and nonhypertensive HFS. Discussion. Although the prevalence of hypertension in HFS was higher (42.7% versus 39.1%) compared to controls matched for age, sex, and BMI, the difference was not significant (see the table). Stratifying the patients and controls by age groups also did not reveal any significant difference of hypertension between the two groups. Similar conclusions were found when we compared the findings with our population controls (National Health Population Survey, 1998). A large difference in the hypertension prevalence (40% to 50%) between HFS and controls would be necessary to impact our clinical management of the majority of HFS patients. As there was probably a selection bias for the more severe HFS patients in the movement disorder clinic, a higher than expected prevalence of hypertension in HFS would have been observed. However, our findings suggested that hypertension was not a major risk factor for HFS in our population. Unlike previous studies,3,5,6 we used controls matched for age, sex, and BMI, and our patients were investigated with highresolution MRI/MRA techniques highly sensitive for NVC in HFS. The availability of population control data based on similar methodology has helped to increase the power of analysis. We did not have imaging data in our study controls and could not investigate the association of NVC of the REZ of the seventh nerve or the ventrolateral medulla with hypertension. However, in a previous MRI/MRA study, NVC of the seventh cranial nerve in our control population was 25%,7 much lower than the 95.1% and 92.7% in our hypertensive and nonhypertensive HFS patients in this study. This suggests that NVC of the REZ of the seventh cranial nerve is unlikely to be associated with hypertension. Our results suggest that there may be etiologic differences among the races. It is possible that anatomic differences in the

Depression, anxiety, and apathy in Parkinson's disease: insights from neuroimaging studies

Depression, anxiety and apathy are common mood disturbances in Parkinsons disease (PD) but their pathophysiology is unclear. Advanced neuroimaging has been increasingly used to unravel neural substrates linked to these disturbances. A systematic review is provided of neuroimaging findings in depression, anxiety and apathy in PD. A PubMed, MEDLINE and EMBASE search of peer‐reviewed original research articles on these mood disturbances in PD identified 38 studies on depression, eight on anxiety and 14 on apathy in PD. Most of the imaging studies used either position emission tomography or single‐photon emission computed tomography techniques. These studies generally suggest increased neural activity in the prefrontal regions and decreased functional connectivity between the prefrontal−limbic networks in depressed patients. Functional imaging studies revealed an inverse correlation between dopaminergic density in the caudate and putamen with the severity of anxiety in PD. There was no consistent correlation between dopaminergic density of thalamus and anxiety. Studies demonstrated both positive and inverse correlations between apathy and metabolism or activity in the striatum, amygdalar, prefrontal, temporal and parietal regions. The clinical variability of study subjects and differences in image pre‐processing and analytical strategies may contribute to discrepant findings in these studies. Both nigrostriatal and extra‐nigrostriatal pathways (in particular the frontal region and its connecting areas) are affected in mood disorders in PD. Identifying the relative contributions of these neural pathways in PD patients with overlapping motor and mood symptoms could provide new pathophysiological clues for the development of better therapeutic targets for affected patients.

Acute ophthalmoparesis in the anti-GQ1b antibody syndrome: electrophysiological evidence of neuromuscular transmission defect in the orbicularis oculi.

Objective: To prospectively study anti-GQ1b antibody positive cases of acute ophthalmoparesis (AO) clinically and electrophysiologically. Methods: Nine consecutive cases presenting with predominantly acute ophthalmoplegia were assessed clinically and had stimulated single fibre electromyography (SFEMG) of the orbicularis oculi at presentation. All had magnetic resonance imaging brain scans and anti-GQ1b antibody titres determined. Results: Four cases had elevated anti-GQ1b antibody titres and abnormal SFEMG studies, which improved in tandem with clinical recovery over three months. Five other anti-GQ1b antibody negative cases were diagnosed as diabetic related cranial neuropathy, idiopathic cranial neuropathy, ocular myasthenia gravis, and Tolosa-Hunt syndrome. All five cases showed complete recovery over a three month period. Conclusions: This study demonstrated electrophysiologically the dynamic improvement of neuromuscular transmission of anti-GQ1b antibody positive cases of AO, in tandem with clinical recovery. SFEMG is of value in differentiating weakness due to neuromuscular transmission defect from neuropathy in these clinical situations.

Evolving spectrum of movement disorders in extrapontine and central pontine myelinolysis

Extrapontine (EPM) and central pontine myelinolysis (CPM) are rare and frequently related to rapid correction of hyponatremia. We describe a 60-year-old woman who developed an unusual evolving spectrum of movement disorders secondary to EPM and CPM following intravenous sodium replacement therapy for severe hyponatremia. She presented initially with confusion, generalized coarse postural limb tremor, myoclonic jerks and quadriparesis. Subsequently her mental state improved and her tremor and weakness resolved. Over the following months, she developed progressive painful dystonia of her facial musculature and lower limbs. This gradually became generalized and associated with choreoathethosis in her limbs. In addition, she had increasing bradykinesia and rigidity, which responded poorly to levodopa treatment. Our case illustrates that while the myelin destruction occurs during the initial insult of the osmotic demyelinating process, its delayed clinical effects resulting from ineffective reorganization of neuronal structures may be progressive, evolve with time, and difficult to treat.

Three-dimensional MR volumetric analysis of the posterior fossa CSF space in hemifacial spasm

Background: We hypothesize that a smaller posterior fossa (PF) CSF space may be a risk factor for hemifacial spasm (HFS). Objective: We conducted a case-control 3-dimensional magnetic resonance (MR) volumetric study in patients with HFS and determined the clinical predictive factors of PF CSF volume. Methods: Patients with clinically diagnosed HFS and controls matched for age, sex, race, and hypertension underwent MRI/magnetic resonance angiography examination. The PF CSF space was segmented and quantified on a heavily T2-weighted high-resolution 3-dimensional MR volume slab, centered over the porus acusticus. Results: Eighty-two study subjects (41 patients and 41 controls) were included. The mean PF CSF volume in patients with HFS and controls was 17,303.0 ± 3,900.0 vs 19,216.0 ± 3,912.0 mm3. The mean volume in patients with HFS was 11.4% smaller than in controls (p = 0.015). Analysis of differences between individually matched pairs and controls also revealed that PF CSF for controls was larger than that for patients with HFS (p = 0.007). A multivariate linear regression analysis revealed that a small PF CSF volume was associated with HFS (p = 0.01). Decreasing age (p = 0.001) and female gender (p < 0.0005), but not hypertension (p = 0.892), were also found to be predictors of a low PF CSF volume. Conclusions: Our results showed that the posterior fossa (PF) CSF volume was lower in patients with HFS compared with matched controls. HFS, female gender, and younger age were associated with smaller PF CSF volume. These observations could explain the strong female preponderance in both clinic- and population-based epidemiologic studies.

Reversible parkinsonism in systemic lupus erythematosus.

Parkinsonism as a manifestation of central nervous system (CNS) lupus is extremely rare. We report the first patient with systemic lupus erythematosus (SLE) who developed a reversible parkinsonian syndrome associated with enhancing subcortical lesions on magnetic resonance imaging (MRI). Following treatment with prednisolone and cyclophosphamide, her bradyphrenia, bradykinesia, hypophonia, rigidity, and abnormal gait progressively improved. Three months after she commenced treatment, repeat MRI scanning demonstrated resolution of the abnormal subcortical white matter enhancement. Our case illustrates unusual clinico-radiologic correlates of reversible parkinsonism in a SLE patient; these findings suggest that disruption of the subcortical frontal pathways may be a possible pathophysiologic mechanism for parkinsonism in cerebral lupus.

Severe bruxism following basal ganglia infarcts: insights into pathophysiology

Bruxism characterized by clenching and grinding of teeth can lead to toothwear, headaches and depression. While bruxism has been associated with a number of neurological diseases, it has not been highlighted following cerebral infarction. An elderly man presented with an acute onset of tooth grinding and jaw clenching associated with dysarthria. His bruxism was worse during the day and resolved during sleep. He had frequent jaw aches, headaches and swallowing difficulty. Examination demonstrated the presence of dysarthria with jaw clenching and tooth grinding, producing persistent high pitch and loud squeaky sounds. A magnetic resonance imaging and angiography examination revealed a recent infarct in the right thalamus. In addition, chronic lacunar infarcts were present in the bilateral caudate nuclei with severe basilar artery stenosis. He was successfully treated with botulinum toxin. We discuss the pathophysiologic mechanisms of bruxism associated with basal ganglia infarcts. Dysfunction of the efferent and/or afferent thalamic or striatopallidal tracts may play a role in bruxism. Early recognition of bruxism following stroke could reduce unnecessary suffering since the condition can be effectively treated.

Transcallosal diffusion tensor abnormalities in predominant gait disorder parkinsonism

BACKGROUND There have been no previous diffusion tensor imaging (DTI) studies comparing Parkinsons disease (PD) with postural instability and gait disorder (PIGD) parkinsonism. OBJECTIVE Utilizing DTI with 2-region tractography, we conducted a case control study to determine if different brain regions representing the neural network of the motor system are differentially affected in PIGD compared to PD and controls. METHODS On a 3 T MR machine, using manual ROI (regions of interest) we determined the fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values on DTI in anatomical brain regions representing the extrapyramidal, pyramidal, and transcallosal tracts, aided by 2-region tractography. FA and ADC were correlated with the Tinetti score (measure of gait and balance). RESULTS Sixty-five subjects (21 PD, 25 PIGD, 19 controls) were included in the analysis. We demonstrated greater ADC abnormalities in the extrapyramidal, pyramidal and transcallosal motor systems in PIGD compared to controls. Multivariate analysis taking into consideration various clinical variables showed that the FA (p = 0.02) and ADC (p = 0.001) values in the corpus callosum body differentiated PIGD from PD. PIGD with low Tinetti score had a lower FA (p = 0.02) and a higher ADC value (corpus callosum body) (p = 0.03) compared to those with a high score. CONCLUSIONS We demonstrated for the first time that DTI abnormalities along the transcallosal motor tract in the body of the corpus callosum, but not the substantia nigra, differentiated PIGD from PD, and the degree of corpus callosum body abnormality correlated with the Tinetti score (a measure of risk of falls).