PET and SPECT Imaging in Hyperkinetic Movement Disorders

Movement disorders can be classified in hypokinetic (e.g., Parkinson's disease, PD) and hyperkinetic disorders (e.g., dystonia, chorea, tremor, tics, myoclonus, and restless legs syndrome). In this chapter, we will discuss results from positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging studies in patients with tremor, tics, myoclonus, and restless legs syndrome. Most studies in patients with tremor included patients with essential tremor (ET): a bilateral, largely symmetric, postural or kinetic tremor mainly involving the upper limbs and sometimes the head. Other studies evaluated patients with orthostatic tremor (OT): an unusually high frequent tremor in the legs that mainly occurs when patients are standing still. Increased regional cerebral blood flow (rCBF) and increased glucose metabolism have been found in the cerebellum, sensorimotor cortex, and thalamus in both patients with ET and OT compared to controls. Both PET and SPECT studies have evaluated the dopamine system in patients with ET and OT. Most imaging studies in patients with ET showed no, or only subtle loss of striatal tracer binding to the dopamine transporter indicating that ET is not characterized by nigrostriatal cell loss. The serotonin and/or gamma-aminobutyric acid (GABA) systems may play a role in the pathophysiology of ET. PET and SPECT imaging of the dopamine and serotonin system in patients with OT showed no abnormalities. Tics, the clinical hallmark of Gilles de la Tourette syndrome (TS), are relatively brief and intermittent involuntary movements (motor tic) and sounds (phonic tic). The essential features of tics are that (1) they can be temporarily suppressed; after suppression a rebound usually occurs with a flurry of tics; (2) the patient experiences an urge to tic, and (3) the tic is followed by a short moment of relief. Using 18F-FDG PET, it was shown that TS is a network disorder where multiple brain areas are active or inactive at the same time. The exact composition of this network is yet to be determined. Using rCBF PET and SPECT many brain regions were found to be abnormal, however, tics mostly correlated with hypoperfusion of the caudate nucleus and cingulate cortex. Both dopamine and serotonin are likely to play a role in the pathophysiology of TS. It is hypothesized that TS is characterized by low serotonin levels that modulate increased phasic dopamine release. Myoclonus is defined as a brief muscle jerk and occurs in many neurologic and non-neurologic disorders. Imaging with PET and SPECT in patients with myoclonus mainly showed abnormalities consistent with the underlying disorder. We described PET and SPECT imaging results in patients in which myoclonus was a prominent symptom. Hypoperfusion and/or hypometabolism of the frontoparietal cortex was found in patients with negative epileptic myoclonus, Alzheimer's disease, corticobasal degeneration, Creutzfeldt-Jakob disease, fatal familiar insomnia, and posthypoxic myoclonus. Other findings that were frequently reported were decreased rCBF and/or glucose metabolism in the cerebellum and thalamus and abnormalities in the dopamine system. Restless legs syndrome (RLS) is defined as an urge to move the legs accompanied with an unpleasant sensation in the legs or in another body part that is especially present during the evening and night and that can be accompanied by periodic limb movements in sleep (PLMS). Imaging studies in these patients have mainly focused on the dopamine system. Most PET studies found decreased tracer binding to the dopamine transporter, although this was not found in SPECT studies. Both PET and SPECT studies showed conflicting results regarding dopamine D2/3 receptor binding: both increased and decreased tracer binding was reported. Furthermore, it is likely that the serotonin and opioid systems also play a role in the pathophysiology of RLS.</p

Liver transplantation as a rescue therapy for severe neurologic forms of Wilson disease

OBJECTIVE: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation. METHODS: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed. RESULTS: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p \textless 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death. CONCLUSIONS: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment

Bipolar disorders and Wilson’s disease

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to determine the risk for Bipolar Disorder (BD) in Wilson’s disease (WD) and to measure the impaired Quality of Life (QL) in BD with WD using standardized psychiatric diagnostic tools and a case control design.</p> <p>Methods</p> <p>This was a case control study. The cases were 23 consecutive patients with WD treated at the University Hospital in Cagliari, Italy, and the controls were 92 sex- and age-matched subjects with no diagnosis of WD who were randomly selected from a database used previously for an epidemiological study. Psychiatric diagnoses according to DSM-IV criteria were determined by physicians using structured interview tools (ANTAS-SCID). QL was measured by means of SF-12.</p> <p>Results</p> <p>Compared to controls, WD patients had lower scores on the SF-12 and higher lifetime prevalence of DSM-IV major depressive disorders (OR = 5.7, 95% CI 2.4–17.3) and bipolar disorders (OR = 12.9, 95% CI 3.6–46.3). BD was associated with lower SF-12 in WD patients.</p> <p>Conclusions</p> <p>This study was the first to show an association between BD and WD using standardized diagnostic tools and a case control design. Reports in the literature about increased schizophrenia-like psychosis in WD and a lack of association with bipolar disorders may thus have been based on a more inclusive diagnosis of schizophrenia in the past. Our findings may explain the frequent reports of loss of emotional control, hyperactivity, loss of sexual inhibition, and irritability in WD patients. This study was limited by a small sample size.</p

PET and SPECT Imaging in Hyperkinetic Movement Disorders.

Movement disorders can be classified into hypokinetic (e.g., Parkinson’s disease; PD) and hyperkinetic disorders (e.g., dystonia, chorea, tremor, tics, myoclonus, and restless legs syndrome). In this chapter, we will discuss results from PET and SPECT imaging studies in patients with tremor, tics, myoclonus, and restless legs syndrome. Most studies in patients with tremor included patients with essential tremor (ET): a bilateral, largely symmetric postural or kinetic tremor involving the hands and forearms and sometimes the head. Other studies evaluated patients with orthostatic tremor (OT): an unusually high frequent tremor in the legs that mainly occurs when patients are standing still. Increased rCBF and increased glucose metabolism have been found in the cerebellum, sensorimotor cortex, and thalamus in both patients with ET and OT compared to controls. Both PET and SPECT studies have evaluated the dopamine system in patients with ET and OT. Most imaging studies in patients with ET showed no or only subtle loss of striatal tracer binding to the dopamine transporter indicating that ET is not characterized by nigrostriatal cell loss. The serotonin and/or GABA systems may play a role in the pathophysiology of ET. PET and SPECT imaging of the dopamine and sero- tonin system in patients with OT showed no abnormalities. Tics, the clinical hallmark of Gilles de la Tourette syndrome (TS), are rela- tively brief and intermittent involuntary movements (motor tic) and sounds (pho- nic tic). The essential features of tics are that (i) they can be temporarily suppressed (after suppression a rebound usually occurs with a flurry of tics), (ii) the patient experiences an urge to tic, and (iii) the tic is followed by a short moment of relief. Using FDG and PET, it was shown that TS is a network disor- der where multiple brain areas are active or inactive at the same time. The exact composition of this network is yet to be determined. Using rCBF PET and SPECT, many brain regions were found to be abnormal; however, tics mostly correlated with hypoperfusion of the caudate nucleus and cingulate cortex. Both dopamine and serotonin are likely to play a role in the pathophysiology of TS. It is hypothesized that TS is characterized by low serotonin which modulates increased phasic dopamine release. Myoclonus is defined as a brief muscle jerk and occurs in many neurologic and non-neurologic disorders. Imaging with PET and SPECT in patients with myoclonus mainly shows abnormalities consistent with the underlying disorder. We described PET and SPECT imaging results in patients in which myoclonus was a prominent symptom. Hypoperfusion and/or hypometabolism of the fron- toparietal cortex was found in patients with negative epileptic myoclonus, Alzheimer’s disease, corticobasal degeneration, Creutzfeldt-Jakob disease, fatal familiar insomnia, and posthypoxic myoclonus. Other findings that were fre- quently reported were decreased rCBF and/or glucose metabolism in the cerebel- lum and thalamus and abnormalities in the dopamine system. Restless legs syndrome (RLS) is defined as an urge to move the legs accom- panied with an unpleasant sensation in the legs or in another body part that is especially present during the evening and night and that can be accompanied by periodic limb movements in sleep (PLMS). Imaging studies in these patients have mainly focused on the dopamine system. Most PET studies found decreased tracer binding to the dopamine transporter, although this was not found in SPECT studies. Both PET and SPECT studies showed conflicting results regarding dopamine D2/3 receptor binding: both increased and decreased tracer binding was reported. Furthermore, it is likely that the serotonin and opioid systems also play a role in the pathophysiology of RLS