The progressive myoclonus epilepsies (PMEs) are a group of predominantly recessive disorders that present with action myoclonus, tonic-clonic seizures, and progressive neurological decline. Many PMEs have similar clinical presentations yet are genetically heterogeneous, making accurate diagnosis difficult. A locus for PME was mapped in a consanguineous family with a single affected individual to chromosome 17q21. An identical-by-descent, homozygous mutation in GOSR2 (c.430G>T, p.Gly144Trp), a Golgi vesicle transport gene, was identified in this patient and in four apparently unrelated individuals. A comparison of the phenotypes in these patients defined a clinically distinct PME syndrome characterized by early-onset ataxia, action myoclonus by age 6, scoliosis, and mildly elevated serum creatine kinase. This p.Gly144Trp mutation is equivalent to a loss of function and results in failure of GOSR2 protein to localize to the cis-Golgi.

Background: Parkinson's disease (PD) is the second most common neurodegenerative disorder. One of the most widely used techniques to diagnose PD is a Single Photon Emission Computer Tomography (SPECT) scan to visualise the integrity of the dopaminergic pathways in the brain. Despite this there remains some discussion on the value of SPECT in the differential diagnosis of PD. We did a meta-analysis of all the existing literature on the diagnostic accuracy of both pre-and post-synaptic SPECT imaging in the differential diagnosis of PD.

Background: SPECT is one of the most employed techniques in the diagnostic workup of idiopathic Parkinson’s disease (IPD). Despite its widespread use, the exact diagnostic accuracy of this technique in parkinsonian syndromes remains controversial. Methods: In this study, we investigated the diagnostic accuracy of an initial ¹²³I-ioflupane (FP-CIT) and/or ¹²³I-iodobenzamide (IBZM) SPECT to differentiate between IPD and other parkinsonian disorders. 248 patients underwent a SPECT scan because of an as yet unclassified parkinsonian syndrome in our clinic between 2001 and 2006. Gold standard was the clinical diagnosis derived from the latest available clinical record, or, when this was not possible, a new complete physical and neurological examination by a blinded movement disorder specialist neurologist. Mean follow-up between SPECT and the latest clinical information was 18 months (range 3 months to 5 years). Results: 223 of the 248 patients were clinically definitely diagnosed after follow-up: IPD 127, atypical parkinsonian syndromes (APS) 27, essential tremor (ET) 22, vascular parkinsonism (VP) 16, drug-induced parkinsonism (DIP) 5, doubt between PD and APS 2, other diseases without dopaminergic involvement 24. The mean odds ratio (95% CI) for FP-CIT SPECT’s ability to distinguish between IPD and ET was 82 (11–674); between IPD and VP 61 (8–490); between IPD and DIP 36 (2–697) and between IPD and APS was 1 (0–4). The odds ratio for the IBZM SPECT tracer to differentiate between IPD and APS was 7 (2–17). Conclusions: FP-CIT SPECT is accurate to differentiate patients with IPD from those with ET, and IPD from VP and DIP. The accuracy of both FP-CIT and IBZM SPECT scans to differentiate between IPD and APS is low.

ObjectiveNumerous ultrasound studies have suggested that a typical enlarged area of echogenicity in the substantia nigra (SN+) can help diagnose idiopathic Parkinson's disease (IPD). Almost all these studies were retrospective and involved patients with well-established diagnoses and long-disease duration. In this study the diagnostic accuracy of transcranial sonography (TCS) of the substantia nigra in the patient with an undiagnosed parkinsonian syndrome of recent onset has been evaluated.DesignProspective cohort study for diagnostic accuracy.SettingNeurology outpatient clinics of two teaching hospitals in the Netherlands.Patients196 consecutive patients, who were referred to two neurology outpatient clinics for analysis of clinically unclear parkinsonism. Within 2 weeks of inclusion all patients also underwent a TCS and a 123I-ioflupane Single Photon Emission CT (FP-CIT SPECT) scan of the brain (n=176).Outcome measuresAfter 2 years, patients were re-examined by two movement disorder specialist neurologists for a final clinical diagnosis, that served as a surrogate gold standard for our study.ResultsTemporal acoustic windows were insufficient in 45 of 241 patients (18.67%). The final clinical diagnosis was IPD in 102 (52.0%) patients. Twenty-four (12.3%) patients were diagnosed with atypical parkinsonisms (APS) of which 8 (4.0%) multisystem atrophy (MSA), 6 (3.1%) progressive supranuclear palsy (PSP), 6 (3.1%) Lewy body dementia and 4 (2%) corticobasal degeneration. Twenty-one (10.7%) patients had a diagnosis of vascular parkinsonism, 20 (10.2%) essential tremor, 7 (3.6%) drug-induced parkinsonism and 22 (11.2%) patients had no parkinsonism but an alternative diagnosis. The sensitivity of a SN+ for the diagnosis IPD was 0.40 (CI 0.30 to 0.50) and the specificity 0.61 (CI 0.52 to 0.70). Hereby the positive predictive value (PPV) was 0.53 and the negative predictive value (NPV) 0.48. The sensitivity and specificity of FP-CIT SPECT scans for diagnosing IPD was 0.88 (CI 0.1 to 0.95) and 0.68 (CI 0.58 to 0.76) with a PPV of 0.75 and an NPV of 0.84.ConclusionsThe diagnostic accuracy of TCS in early stage Parkinson's disease is not sufficient for routine clinical use.Clinicaltrials.gov identifierNCT0036819

SN-TCD accurately differentiates between patients with IPD and healthy controls, but not between patients with IPD and APS. LN-TCD is only moderate accurate to delineate IPD from APS, but combinations of SN- and LN-TCD may be more promising. RN-TCD has only marginal diagnostic accuracy in diagnosing depression in IPD and non-IPD patients. Before TCD can be implicated, more research is needed to standardize the TCD technique, to investigate the TCD in non-research settings and to determine the additional value of TCD compared with currently used clinical techniques like SPECT imaging.