Tomasz Litwin

Wilson’s disease—cause of mortalityin 164 patients during 1992–2003observation period

AbstractWe studied the cause of death in a consecutive series of 164 patients with Wilson’s disease (WD) diagnosed over an 11 year period. A total of 20 [12% (95% CI 10.3–16.0)] died during the observation period. The relative survival rate of all patients in our group was statistically smaller than in Polish population. The main cause of death was the diagnosis in advanced stage of disease, but in six patients presenting with mild signs, we observed the progression of the disease despite treatment. There was no difference in mortality rate in patients treated with dpenicillamine or zinc sulphate as initial therapy.The prognosis for survival in the majority of WD patients is favourable, provided that therapy is introduced early.

New approach to the rehabilitation of post-stroke focal cognitive syndrome: Effect of levodopa combined with speech and language therapy on functional recovery from aphasia

OBJECTIVE Few studies confirm that pharmacological treatments support post-stroke recovery. The purpose of this study was to determine whether the combination of levodopa with language therapy improves aphasia rehabilitation. METHODS We did a prospective, randomized, placebo-controlled, double-blind study in which twenty patients received levodopa before each language therapy session, and an additional 19 received a placebo. Language training was provided during a 3-week period. The efficacy variables were changes from baseline in Boston Diagnostic Aphasia Examination (BDAE) scores. RESULTS Patients receiving levodopa experienced greater language improvement in verbal fluency and repetition, compared to patients receiving placebo. Improvement was particularly distinct in patients with anterior lesions. CONCLUSIONS Supplementing language therapy with levodopa may improve recovery from aphasia in patients with frontal lesions.

Brain metal accumulation in Wilson's disease.

INTRODUCTION Brain metal accumulation is suggested in the pathogenesis of numerous neurodegenerative disorders. In Wilsons disease (WD), only copper has been examined. The aim of the present study was to evaluate the copper, iron, manganese, and zinc concentrations in autopsy tissue samples from the brains of WD patients. METHODS The study material consisted of 17 brains (12 WD patients, 5 controls) obtained at autopsy. Samples were taken from four different regions of each brain: frontal cortex, putamen, pons, and nucleus dentatus. The copper, manganese, and zinc content were determined using inductively coupled plasma mass spectrometry, and iron was assessed using flame atomic absorption spectroscopy. The results were analyzed according to select clinical variables. RESULTS Copper content was increased homogenously in all investigated structures of the WD brains compared to controls (41.0 ± 18.6 μg/g vs.5.4 ± 1.8 μg/g; P<0.01). The mean concentrations of iron, manganese, and zinc were similar in WD and controls, but the iron level in the nucleus dentatus was higher in WD compared to controls (56.8 ± 14.1 μg/g vs. 32.6 ± 6.0 μg/g; P<0.05). Gender, age, and type and duration of WD treatment did not impact brain metals storage, but some correlations between the duration of the disease and copper and iron accumulation were observed. CONCLUSIONS During the course of WD, copper accumulates equally in different parts of the brain. Zinc and manganese do not seem to be involved in WD pathology, but increased levels of iron were found in the nucleus dentatus. Thus, additional studies of brain iron accumulation in WD are needed.

Wilson Disease and Other Neurodegenerations with Metal Accumulations

Trace elements, such as iron, copper, manganese, and calcium, which are essential constituents necessary for cellular homeostasis, become toxic when present in excess quantities. In this article, we describe disorders arising from endogenous dysregulation of metal homeostasis leading to their tissue accumulation. Although subgroups of these diseases lead to regional brain metal accumulation, mostly in globus pallidus, which is susceptible to accumulate divalent metal ions, other subgroups cause systemic metal accumulation affecting the whole brain, liver, and other parenchymal organs. The latter group comprises Wilson disease, manganese transporter deficiency, and aceruloplasminemia and responds favorably to chelation treatment.

Neurological presentation of Wilson's disease in a patient after liver transplantation.

We report of a 32‐year‐old man who showed dystonic symptoms within few days after liver transplantation (LT). The clinical, biochemical, and, finally, genetic evaluation confirmed Wilsons disease diagnosis in this patient. We suspect that extrapyramidal signs in this case could be a result of acute brain injury because of the massive copper release from liver to the circulation just before and during LT.

Lack of experience of intravenous thrombolysis for acute ischaemic stroke does not influence the proportion of patients treated

Objectives: To determine the eligibility of patients with ischaemic stroke admitted to the 2nd Department of Neurology, Institute of Psychiatry and Neurology, Warsaw, Poland, for intravenous thrombolysis; to identify the major exclusions and assess whether organisational changes in the in-hospital stroke pathway and informative campaign in the local community and medical services can increase the number of patients treated; and to establish whether lack of previous experience with thrombolytic treatment or trials is predictive of the low proportion of patients treated. Methods: A survey of the database of patients with stroke admitted during the first 30 months after the introduction of intravenous thrombolysis for acute ischaemic stroke was conducted to search for all eligible patients. This included patients admitted within 2 h of symptom onset (assuming a 1 h door-to-needle time), age <80 years, National Institute of Health Stroke Scale (NIHSS) Score of 5–22, seizures at onset, platelet count >100 000/ml, glycaemia 50–400 mg/dl and international normalised ratio (INR) <1.6. The number of eligible patients was compared with the number actually treated. Results: 745 patients with acute ischaemic stroke were admitted during the study period. 18.4% were admitted within 2 h of symptom onset, 71% were aged <80 years, 55.4% had an NIHSS score between 5 and 22, 96.1% had INR <1.6, 98.9% had a platelet count >100 000/ml, 99.4% had blood glucose concentrations of 50–400 mg/dl and 97.4% had no seizures at onset. After adjusting for all inclusion criteria, 7.1% of the patients were found to be potentially eligible and 8.7% were actually treated (p = 0.25). Of the 65 treated patients, 63.1% were independent after 3 months, 16.9% died and none had a symptomatic intracranial haemorrhage. Conclusions: The proportion of patients with ischaemic stroke treated with intravenous thrombolysis in a previously inexperienced centre was not lower than in other centres and in countries where this treatment has been provided for a longer period of time. The number of patients treated was higher than that estimated mainly owing to organisational changes introduced in our centre, allowing treatment of those admitted between 2 and 3 h after symptom onset.

Early neurological worsening in patients with Wilson's disease

BACKGROUND Early neurological worsening during treatment initiation for Wilsons disease (WD) is an unresolved problem. Our aim was to establish the frequency and outcome of early neurological worsening in patients with WD. METHODS We analyzed 143 symptomatic patients diagnosed with WD between 2005 and 2009. Early neurological deterioration was based on worsening on the Unified Wilsons Disease Score Scale, scored at baseline through 6 months or occurrence of new neurological symptoms. Reversibility of worsening was followed up to 24 months. RESULTS Early neurological worsening was observed in 11.1% (16/143) and involved only patients with neurological signs at diagnosis. Mean time to worsening from treatment initiation was 2.3 ± 1.9 months. Neurological deterioration was completely reversible in 53% (8/15) and partially in 13% (2/15) of patients over 9.2 ± 5.2 months. Patients who experienced early deterioration had significantly more severe baseline neurological deficit, higher prevalence of thalamic (66% vs 29%) and brain stem (73% vs 33%) lesions seen on baseline magnetic resonance imaging, and more often used concomitant dopamine receptor antagonists (46% vs 5%). Disease duration, treatment type (d-penicillamine or zinc sulfate), type of neurological manifestations, initial copper metabolism results, and liver function parameters did not differ between evaluated groups. CONCLUSIONS Neurological worsening at the beginning of anti-copper therapy may occur in over 10% of WD patients. Special attention should be paid to those with severe initial neurological manifestations, advanced brain injury and using dopamine receptor antagonists. Type of anti-copper therapy did not show clear association with early neurological worsening.

Diverse attention deficits in patients with neurologically symptomatic and asymptomatic Wilson's disease.

OBJECTIVE Cognitive deficits in patients with Wilsons disease (WD) have been reported in several studies, but there was no detailed analysis of the various components of attention, one of the most significant factors of the executive system. Our study determined the pattern of deficits in attention subsystems in WD patients, including selective attention, divided attention, attention switching, and sustained attention. METHOD We examined 67 WD patients using the Test of Everyday Attention (TEA)-33 participants with neurological symptoms and 34 who were neurologically asymptomatic, but most with mild hepatic dysfunctions. The results were compared with 43 matched healthy controls. RESULTS The group of WD patients with neurological symptoms performed significantly worse (p < .05) in all components of attention: sustained attention, selective attention, divided attention, and attentional switching. WD patients without neurological symptoms exhibited significantly lower results in one component-sustained attention (p < .05). None of the TEA subtests scores were associated significantly with Unified Wilsons Disease Rating Scale scores, which may reflect that the cognitive and neurological consequences of WD are relatively independent. CONCLUSIONS We found a deficiency in all components of attention in neurological WD patients. The most frequently disturbed function was attention switching. Relatively milder deficits concerned divided, selective, and sustained attention. These are all abilities creating the core of the executive system and are regulated by subcortical prefrontal circuits, which are usually dysfunctional in WD patients. In neurologically asymptomatic patients, an isolated deficit of sustained attention occurs; this may be a sign of mild hepatic encephalopathy.

Encephalopathy in Wilson Disease: Copper Toxicity or Liver Failure?

Hepatic encephalopathy (HE) is a complex syndrome of neurological and psychiatric signs and symptoms that is caused by portosystemic venous shunting with or without liver disease irrespective of its etiology. The most common presentation of Wilson disease (WD) is liver disease and is frequently associated with a wide spectrum of neurological and psychiatric symptoms. The genetic defect in WD leads to copper accumulation in the liver and later in other organs including the brain. In a patient presenting with Wilsonian cirrhosis neuropsychiatric symptoms may be caused either by the metabolic consequences of liver failure or by copper toxicity. Thus, in clinical practice a precise diagnosis is a great challenge. Contrary to HE in neurological WD consciousness, is very rarely disturbed and pyramidal signs, myoclonus dominate. Asterixis and many other clinical symptoms may be present in both disease conditions and are quite similar. However details of neurological assessment as well as additional examinations could help in differential diagnosis.

Brain iron accumulation in Wilson disease: a post mortem 7 Tesla MRI - histopathological study.

In Wilson disease (WD), T2/T2*‐weighted (T2*w) MRI frequently shows hypointensity in the basal ganglia that is suggestive of paramagnetic deposits. It is currently unknown whether this hypointensity is related to copper or iron deposition. We examined the neuropathological correlates of this MRI pattern, particularly in relation to iron and copper concentrations.