Dulce Neutel

Substantia nigra neuromelanin magnetic resonance imaging in de novo Parkinson's disease patients

Depigmentation of the substantia nigra (SN) and locus coeruleus (LC) is a conspicuous pathological feature of Parkinsons disease (PD) and is related to the loss of neuromelanin, whose paramagnetic properties result in high signal on specific T1‐weighted magnetic resonance imaging (MRI). Recent studies have suggested that neuromelanin decrease in the SN and LC of PD patients may emerge as a possible diagnostic biomarker. The SN neuromelanin signal in de novo and early stage PD patients was studied to assess its diagnostic accuracy. This is the first study based on a semi‐automated MRI analysis of the neuromelanin signal in de novo PD patients.

Skin cancer and Parkinson's disease

The report of an increased frequency of melanoma during the clinical development of rasagiline prompted a renewed interest in a possible association between skin cancer and Parkinsons disease (PD). The evaluation of this risk ended in a recommendation to perform a periodic dermatological examination as a follow‐up measure of their treatment. The recognition of this safety concern lead to the need to clarify if the risk of skin cancer is indeed associated with PD and if levodopa or other anti‐parkinsonian drugs might contribute to increase such risk. To answer these questions, we critically reviewed all clinical studies available concerning the association between skin cancer and PD. We found 26 studies on cancer occurrence in PD. The best data available suggest the risk of cancer is reduced in PD patients. However, specific cancers like thyroid and the female breast were reported at higher‐than‐expected rates. Additionally, it was suggested that PD patients have a higher frequency of melanoma and non‐melanoma skin cancers than the general population. The data on non‐melanoma skin cancer are less robust than the data on melanoma. Causal factors remain unknown. Due to the weak association between skin cancer and PD, no robust recommendation can be made regarding the need for periodic dermatological screening.

Substantia nigra neuromelanin-MR imaging differentiates essential tremor from Parkinson's disease.

Essential tremor (ET) is a very common movement disorder that has no diagnostic markers. Differentiation with Parkinsons disease (PD) can be clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic resonance imaging (MRI) studies have been able to identify neuromelanin changes in the substantia nigra (SN) of PD patients, but they have thus far not been investigated in ET. In this study, we aimed to characterize neuromelanin‐MR signal changes in ET and evaluate its diagnostic accuracy in the differential diagnosis with PD.

Magnetic resonance correlation of iron content with neuromelanin in the substantia nigra of early‐stage Parkinson's disease

Magnetic resonance (MR) studies have demonstrated a significant reduction of neuromelanin in the substantia nigra (SN) of Parkinsons disease (PD) patients with high accuracy for differential diagnosis compared to non‐PD controls and essential tremor. However, studies state that not knowing how paramagnetic effects of iron influence neuromelanin signal is a limitation. In this study a neuromelanin‐sensitive MR sequence was combined with T2* relaxometry iron quantification analysis to study the SN of early‐stage PD patients to investigate the correlation between these parameters.

Delayed leukoencephalopathy after acute carbon monoxide intoxication

Delayed leukoencephalopathy is an uncommon complication of hypoxic-ischemic events of different etiologies, including carbon monoxide intoxication. We present a case of a 40-year-old male patient who was admitted with rapidly progressive neurocognitive and behavioral deficits. There was a history of accidental carbon monoxide intoxication one month before, presenting with loss of consciousness and short hospitalization, followed by a complete clinical recovery. The imaging studies in the delayed phase depicted confluent, symmetric supra-tentorial white matter lesions in keeping with diffuse demyelinization. Restricted diffusion and metabolite abnormalities in magnetic resonance proton spectroscopy were also seen. The diagnosis of CO-mediated delayed post-hypoxic leukoencephalopathy was assumed after exclusion of other mimickers. Hyperbaric oxygen therapy was tentatively performed and the patient had a favorable clinical and radiological evolution.

Nocturnal agitation in Huntington disease is caused by arousal-related abnormal movements rather than by rapid eye movement sleep behavior disorder.

BACKGROUND Patients with Huntington disease (HD) and their spouses often complain of agitation during sleep, but the causes are mostly unknown. OBJECTIVE To evaluate sleep and nocturnal movements in patients with various HD stages and CAG repeats length. METHODS The clinical features and sleep studies of 29 patients with HD were retrospectively collected (11 referred for genotype-phenotype correlations and 18 for agitation during sleep) and compared with those of 29 age- and sex-matched healthy controls. All patients had videopolysomnography, but the movements during arousals were re-analyzed in six patients with HD with stored video. RESULTS The patients had a longer total sleep period and REM sleep onset latency, but no other differences in sleep than controls. There was no correlation between CAG repeat length and sleep measures, but total sleep time and sleep efficiency were lower in the subgroup with moderate than milder form of HD. Periodic limb movements and REM sleep behavior disorders were excluded, although 2/29 patients had abnormal REM sleep without atonia. In contrast, they had clumsy and opisthotonos-like movements during arousals from non-REM or REM sleep. Some movements were violent and harmful. They might consist of voluntary movements inappropriately involving the proximal part of the limbs on a background of exaggerated hypotonia. Giant (>65 mcV) sleep spindles were observed in seven (24%) patients with HD and one control. CONCLUSION The nocturnal agitation in patients with HD seems related to anosognostic voluntary movements on arousals, rather than to REM sleep behavior disorder and other sleep problems.

Giant cell arteritis with symptomatic intracranial stenosis and endovascular treatment

Giant cell arteritis (GCA) is the commonest systemic vasculitis in adults. It is characterized by granulomatous inflammation in the wall of medium size and large arteries. Classically, it affects external carotid branches, namely, superficial temporal artery. It is a rare cause (3–4 %) of transient ischaemic attacks, and stroke due to carotid and vertebral extracranial stenosis [1, 2]. There are scarce reports of GCA with intracranial stenosis and stroke [3, 4]. Here, we report on a 65-year-old black man with a medical history of hypertension, dyslipidemia, congenital 6-phosphogluconate dehydrogenase, and GCA confirmed by temporal artery 3 months before, presented to emergency department with sudden language and right motor deficit, while withdrawing corticosteroid treatment but still under prednisolone (PDN) 50 mg/daily, acetylsalicylic acid (AAS) 100 mg/daily and lisinopril 5 mg/daily. On neurological examination, there was anomic dysphasia, right hemiparesis and homolateral upper limb ataxia. Laboratory examination showed an elevated erythrocyte sedimentation rate (ESR) (57 mm/h) but autoimmune, cerebrospinal fluid and hemoglobin electrophoresis studies were normal. Diffusion-weighted MRI showed acute left middle cerebral artery watershed infarcts (Fig. 1a) and right posterior inferior cerebellar artery (PICA) ischemia. Doppler ultrasonography (US) of the temporal arteries showed bilateral periluminal hypoechogenic halo. Cervical US and Transcranial Doppler (TCD) suggested distal preocclusive stenosis of the left internal carotid artery (ICA) and a severe stenosis of the cavernous segment of the right ICA. Angio-MRI showed the progressive left ICA stenosis from its origin, with pre-occlusive stenosis in the cavernous and supraclinoid segments; occlusion of V4 segments of both vertebral arteries and of the inferior third of the basilar artery (Fig. 1b). Furthermore, conventional angiogram showed a segmental stenosis of the right ICA petrous segment (the flow came from the anterior circulation bilaterally; the posterior circulation fed via the right posterior communicating; there was a reverse flow in the basilar artery filling the left anterior inferior cerebellar artery and PICA) (Fig. 1c, d). Systemic and brain PET-CT showed decreased uptake of 18FDG in parietal and left occipital cortices and right cerebellar hemisphere; increased uptake in the territory of right superficial temporal and left posterior auricular arteries (Fig. 1f); thoracic and abdominal aorta included iliac and femoral branches and a cardiac MRI (with aortic arch) were unremarkable. Treatment was switched to clopidogrel 75 mg/daily, simvastatin 20 mg/daily, and PDN 1 mg/kg/daily and he was discharge. One month later, he developed recurrent aphasia following iatrogenic hypotension and syncope. ESR was 9 mm/h and TCD was stable. Brain MRI disclosed a new acute stroke, adjacent to the previous lesion. Angioplasty was performed in the supraclinoid segment of left ICA and D. Neutel T. P. e Melo L. Albuquerque Neurology Department, Santa Maria Hospital, CHLN, Lisbon, Portugal

Recovery after copper-deficiency myeloneuropathy in Wilson's disease.

Wilson’s disease (WD) treatment focuses on removing excess copper from the body and preventing reaccumulation, but there are reports of neuropathy and myeloneuropathy (MN) linked to copper deficiency (CD) induced by excessive depletion [1]. Here we report on a WD patient with MN associated with longstanding CD. The patient is a 36-year-old male diagnosed with WD at 20 years old, having displayed generalized dystonia, bradykinesia and freezing of gait. Clinical stability was achieved with zinc sulphate 150 mg/ day and trientine 500 mg/day. In 2006, he developed low urinary copper (24 h urine copper = 128 lg/24 h, recommended 200–500 lg/24 h; serum copper 6.35 lg/dL) [6], which worsened in the following years. In 2008 he was switched to D-penicillamine 600 mg/day due to drug availability problems. Soon after, he developed a nephrotic syndrome with focal segmental glomerular sclerosis which resolved with corticosteroid therapy and switching back to trientine. In February 2011, he developed subjective numbness of both hands and feet and over the following months worsening of gait with frequent falls. In July 2011 neurological examination revealed de novo algic hypoesthesia of the limbs in a ‘‘glove and stocking’’ pattern, postural and vibratory hypoesthesia of the lower limbs and gait ataxia. Analytical studies revealed low serum and urine copper (serum copper 13.3 lg/dL, urine copper 40.5 lg/24 h), low ceruloplasmin (3.0 mg/dL), normal zinc levels (14.7 lmol/ L) and anemia (Hb 8.2 g/dL). Electromyography with conduction velocities revealed a mixed sensory-motor peripheral neuropathy and spinal MRI showed signs of posterior dorsal cord myelopathy (Fig. 1). Other causes of MN were excluded: both vitamin E and B12 levels were normal, and serological tests for HIV, syphilis and autoantibodies were negative. Therefore, a causal relationship between CD and MN was considered as probable. Trientine (500 mg/day) and zinc sulfate (330 mg/day) were substituted for zinc acetate 100 mg daily, which was progressively reduced and stopped in January 2012, due to persistent CD. Copper deficiency resolved by March 2012 (24 h urinary copper = 97 lg/24 h, recommended B100 lg/24 h for zinc monotherapy) [6]. Parallel improvement of sensorial ataxia allowed recovery of walking capacity without assistance. Spinal MRI showed mild regression of myelopathy signs (Fig. 1). Conduction velocities studies disclosed slight improvement in amplitude of sensory action potentials and conduction velocities (Table 1). At this point, zinc acetate 150 mg/day was reintroduced, and his condition remains stable 1 year after treatment. T. Teodoro (&) D. Neutel P. Lobo I. Conceição M. M. Rosa L. Albuquerque J. J. Ferreira Department of Neurology, Hospital de Santa Maria (CHLN, EPE), Lisbon, Portugal e-mail: tiagoteodoro@gmail.com

Mystery Case: Catathrenia A rare but treatable parasomnia

A 32-year-old man with somatosensory seizures due to bilateral perisylvian polymicrogyria, completely controlled with valproate 1,500 mg/day, presented to the epilepsy clinic with his wife, describing groaning several times a night (video on the Neurology® Web site at Neurology.org). Nocturnal polysomnography showed no epileptic activity and revealed catathrenia (figures 1 and 2). He started continuous positive airway pressure (CPAP) 4–12 cm H2O and this resolved his complaints.

Recurrent Ischemic Stroke in an Adult with Cystinosis: A Clinical-Pathological Case

A 32-year-old woman with infantile nephropathic cystinosis presented with cystinosis and recurrent ischemic stroke. The neuropathological description demonstrates that recurrent stroke was caused by intracranial stenosis and showed evidence of cystinosis brain involvement. There are few reports of cerebrovascular disease in patients with longstanding nephropathic cystinosis. This case reinforces that cerebrovascular disease can be a cause of neurological impairment and disability in patients with longstanding nephropathic cystinosis, with implications on primary stroke prevention strategies in these patients.