Chris Clough

A multicentre longitudinal observational study of changes in self reported health status in people with Parkinson’s disease left untreated at diagnosis

Background: The issue of when to start treatment in Parkinson’s disease (PD) remains controversial. Some favour treatment at diagnosis while others opt for a “wait and watch” policy. The effect of the latter policy on the self reported health status of people with PD is unknown. Aims: To record self reported health status through longitudinal use of a validated PD specific questionnaire (PDQ-39) in untreated PD patients in multiple centres in the UK. To compare patients who were left untreated with those who were offered treatment during follow-up. Methods: A multicentre, prospective, “real life” observational audit based study addressing patient reported outcomes in relation to self reported health status and other sociodemographic details. Results: 198 untreated PD were assessed over a mean period of 18 months. During two follow-up assessments, the self reported health status scores in all eight domains of the PDQ-39 and the overall PDQ-39 summary index worsened significantly (p<0.01) in patients left untreated. In a comparative group in whom treatment was initiated at or soon after diagnosis, there was a trend towards improvement in self reported health status scores after treatment was started. Conclusions: This study addresses for the first time self reported health status, an indicator of health related quality of life, in untreated PD. The findings may strengthen the call for re-evaluation of the policy to delay treatment in newly diagnosed patients with PD.

Late onset levodopa responsive Huntington's disease with minimal chorea masquerading as Parkinson plus syndrome

Huntingtons disease is characterised by hyperkinetic movements, mainly chorea, cognitive dysfunction, and psychiatric abnormalities. Non-dopa responsive parkinsonism occurs in the later stages of choreic disease or as the predominant feature of juvenile patients (Westphal variant). Late onset Huntingtons disease presenting as levodopa responsive parkinsonism is rare. A series of four patients with late onset Huntingtons disease presenting as levodopa responsive parkinsonism and cardiovascular dysautonomia, initially misdiagnosed as multiple system atrophy (MSA) in three patients, is reported. Levodopa treatment did not unmask significant chorea. These cases suggest the presence of a distinct phenotypic variant of Huntingtons disease to be added to the differential diagnosis of other akinetic rigid syndromes.

CT/MR Image Fusion in the Postoperative Assessment of Electrodes Implanted for Deep Brain Stimulation

Background/Aims: Stereotactic postoperative imaging is essential for verification of the position of electrodes implanted for deep brain stimulation (DBS). MRI offers superior visualisation of the DBS targets relative to CT, but previous adverse incidents have heightened concerns about risks of postoperative MRI. Preoperative MRI fused with postoperative CT offers an alternative method for evaluating electrode position, but before this method can be clinically applied, the image registration accuracy must be established. The purpose of this study was to quantitatively assess the accuracy of three different image registration and fusion methods. Methods: Preoperative stereotactic MRI and postoperative stereotactic CT were acquired from 20 patients under- going DBS surgery (35 electrodes in total). The postoperative CT was registered and fused with the preoperative MRI, using three different registration algorithms. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position between the CT and fused CT/MRI was used to evaluate the registration accuracy. Results: The mean error along the lateral, anteroposterior, and vertical axes was 0.5, 0.5, and 1 mm, respectively. Conclusions: CT/MRI fusion provides a safe, practical technique for postoperative identification of DBS electrodes.

Limb contractures in levodopa-responsive parkinsonism: A clinical and investigational study of seven new cases

Abstract We describe six patients with classical levodopa-responsive Parkinson’s disease (PD) and one case of levodopa-responsive familial juvenile dystonia-parkinsonism with fixed contractures of the hands, feet or legs. In most patients contractures became established over a short period (2 months–2 years) but a considerable time after onset of parkinsonism (mean 13 years). Mean disease duration was 17 years, and all patients had severe levodopa-induced dyskinesias, either biphasic or peak dose, in the affected limb prior to onset of the contracture. Nerve conduction studies excluded peripheral ulnar nerve lesions in all patients with one exception, who was found to have a mild bilateral ulnar entrapment neuropathy. Transcranial magnetic stimulation performed in five of the seven patients showed shorter mean central motor conduction time in the affected than in the unaffected limb. Results of magnetic resonance imaging of the brain performed in a subgroup of patients were normal, with no evidence to suggest multiple system atrophy, cerebral infarction or focal abnormalities of the basal ganglia. We conclude that hand and feet contractures are not necessarily restricted to parkinson plus syndromes and may complicate otherwise typical PD in the absence of a structural or peripheral nervous cause. Striatal dopaminergic deficiency, particularly long-standing, may have a role in the pathogenesis of limb contractures in PD.

Cognitive predictors of cognitive change following bilateral subthalamic nucleus deep brain stimulation in Parkinson’s disease

The beneficial effects of deep brain stimulation (DBS) of the subthalamic nucleus (STN) for the motor symptoms in advanced Parkinsons disease (PD) are well established. Early in PD, mild cognitive impairment is present in a proportion of patients. Hence, it can also be present in PD patients considered for DBS. The potential impact of even a modest decline post-surgically is a concern because it could result in impaired cognitive function. Therefore, attempts to determine which pre-operative cognitive measures predict post-operative cognitive change warrant further attention. We report our findings in a cohort of 30 routinely operated non-demented patients who underwent detailed neuropsychological assessments on average 7.1 months before and 9.4 months after STN DBS. We report the individual and group differences pre- and post-DBS. Stepwise regression analysis was used to analyse the best cognitive predictors of post-operative cognitive changes. We describe our data in relation to published normative data. Post-STN DBS, the immediate story recall component of verbal memory was the most affected cognitive function showing a significant decline in its group mean with a large effect size. The best predictors for this change were pre-surgical list learning and Full Scale Intelligence Quotient. These results suggest that non-demented patients, with even mild impairments in both general intellectual functions and list learning, may be at greater risk of decline in other aspects of verbal memory after STN DBS. Pre-existing mild executive dysfunction was not influenced post-operatively. These findings may help selection and consent for STN DBS.

A man who vomited until he couldn't walk

In January, 2010, a 73-year-old man became acutely unwell with a sore throat, unsteadiness, and vomiting while visiting Bhopal, India. Within 12 hours he was unable to stand. He was admitted to a local hospital, where he was noted to have a fl accid tetraparesis. A CSF sample showed raised protein (790 mg/L) and presence of white blood cells (lymphocytes 4, polymorphonuclear cells 3), but no glucose and no organisms on Gram stain or stain for acid-fast bacilli. He was transferred to a tertiary centre in Mumbai where a tracheostomy was done and MRI of the brain showed acute encephalomyelitis of the pons, medulla, and upper cervical cord. He was given intravenous methylprednisolone for 7 days, and then oral prednisolone 60 mg/day. He did not improve and on Feb 6, 2010 was started on a 5 day course of intravenous immunoglobulin. On Feb 24, 2010 he was transferred to London for continuing management. On admission to our hospital, he was alert, with a Glasgow Coma Scale score of 10T. Cranial nerve examination was unremarkable, but he had fl accid muscle tone with Medical Research Council (MRC) grade 0/5 power, and absent refl exes in upper and lower limbs. Sensory examination was normal. He was treated empirically for a bacterial encephalo menin gitic brainstem infection with ceftri axone and amoxicillin, and had a repeat MRI of his brain and cervical cord (fi gure A). Laboratory tests were normal. Follow-up CSF analysis showed white blood cells within normal range, protein 201 mg/L, and glucose 5·1 mmol/L (serum 6·1 mmol/L). Gram stain and tests for oligoclonal bands were negative. CSF was also negative for herpes simplex virus 1 and 2, varicella zoster virus, Ebstein-Barr virus, and enterovirus. Repeat MRI showed residual medullary high T2 signal with cervical cord extension, which was reduced from previous imaging and thought to be infl am matory (fi gure B). Neurophysi ology was done because of persisting fl accid paralysis suggesting periph eral neur opathy or anterior horn disease. Widespread denervation was found and we considered a viral anterior horn myelitis. Type specifi c serology for polioviruses showed past but not recent exposure. Serum taken in March, 2010 was positive by EIA for West Nile virus IgM and IgG, but CSF from the Lancet 2012; 380: 1966