Hypokinetic-rigid Syndrome Research Articles

18F]PM-PBB3-PET Reveals Clinical and [18F]FDG-PET Mimics of 4-Repeat Tauopathy Caused by Creutzfeld-Jakob Disease.

This image depicts [18F] FDG and [18F]PM-PBB3 uptake surface projections of two male patients with complex movement disturbances. They were referred for PET imaging with the suspected diagnosis of a 4-repeat (4R)-tauopathy Figure 1. Patient #1 (79 years) presented with an aggressive, non-levodopa responsive hypokinetic-rigid syndrome with early falls and a vertical supranuclear gaze palsy. Patient #2 (68 years) presented with unusually rapidly progressive dystonia, right-sided rigor, bradykinesia, alien limb phenomenon and action myoclonus of the right arm, likewise without response to levodopa. Disease duration was 11 and 5 months, respectively. CSF levels of tau and amyloid in either patient were not indicative for Alzheimer's disease. In both, [18F] FDG-PET revealed a corticobasal degeneration-like bilateral reduction of cerebral glucose metabolism in frontoparietal cortical areas (arrowheads) and in the thalamus.1 A clear asymmetry to the detriment of the right hemisphere was observed in #1, whereas hypometabolism of the left hemisphere was only slightly pronounced in #2. Subsequent imaging with tau ligand [18F]PM-PBB32 showed elevated binding (arrowheads, asterisks indicate unspecific uptake of the choroid plexus) suggestive for pathological tau aggregates in frontal and parietal areas of #1, supporting the diagnosis of a 4R-tauopathy.2 In contrast, the lack of specific [18F]PM-PBB3 binding in patient #2 questioned the diagnosis of a 4R-tau related corticobasal syndrome (CBS; eg, progressive supranuclear palsy—CBS). Diagnosis of Creutzfeld-Jakob disease in this patient was made via 14–3-3 and PrPSc aggregation assays. In conclusion, [18F]PM-PBB3-PET reveals clinical and [18F] FDG-PET mimics of 4R-tau CBS caused by Creutzfeld-Jakob disease. (1) Research project: A. Conception, B. Organization, C. Execution; (2) Statistical analysis: A. Design, B. Execution, C. Review and critique; (3) Manuscript: A. Writing of the first draft, B. Review and critique. N.S.: 1A, B, 1C, 2C, 3A. G.B.: 1C, 2B, 2C, 3B. P.T.M.: 1B, 2A, 2C, 3B. M.R.: 1B, 2C, 3B. J.B.: 1C, 2A, 2C, 3A. Materials required for the synthesis of [18F] APN-1607 were generously provided by Aprinoia Therapeutics Limited. Open Access funding enabled and organized by Projekt DEAL. Ethical Compliance Statement: The authors confirm that the approval of an institutional review board was not required for this work. Both patients gave written informed consent for the scientific use of imaging and clinical data. Funding Sources and Conflicts of Interest: Nils Schröter, Berta-Ottenstein-Programme for Clinician Scientists, Faculty of Medicine, University of Freiburg. The authors have no potential conflict of interest to report. We confirm that we have read the Journal's position on issues involved in ethical publication and affirm that this work is consistent with those guidelines. Financial Disclosures for the Previous 12 Months: The authors have nothing to disclose.

Spectrum of de novo movement disorders in the setting of COVID-19 infection: Part 1: Pathogenesis and hypokinetic-rigid syndrome

Spectrum of de novo movement disorders in the setting of COVID-19 infection: Part 1: Pathogenesis and hypokinetic-rigid syndrome

A case of treatable encephalopathy, developmental regression, and proximal tremor

Tyrosine hydroxylase (TH) deficiency is an autosomal recessive condition first described as a progressive, early-onset hypokinetic-rigid and dystonic syndrome that was responsive to levodopa. Here we present a child with developmental regression, proximal tremor, and encephalopathy found to have tyrosine hydroxylase deficiency in whom treatment resulted in acquisition of developmental milestones.

Movement Disorders Associated with COVID-19.

As neurological complications associated with COVID-19 keep unfolding, the number of cases with COVID-19-associated de novo movement disorders is rising. Although no clear pathomechanistic explanation is provided yet, the growing number of these cases is somewhat alarming. This review gathers information from 64 reports of de novo movement disorders developing after/during infection with SARS-CoV-2. Three new cases with myoclonus occurring shortly after a COVID-19 infection are also presented. Treatment resulted in partial to complete recovery in all three cases. Although the overall percentage of COVID-19 patients who develop movement disorders is marginal, explanations on a probable causal link have been suggested by numerous reports; most commonly involving immune-mediated and postinfectious and less frequently hypoxic-associated and ischemic-related pathways. The current body of evidence points myoclonus and ataxia out as the most frequent movement disorders occurring in COVID-19 patients. Some cases of tremor, chorea, and hypokinetic-rigid syndrome have also been observed in association with COVID-19. In particular, parkinsonism may be of dual concern in the setting of COVID-19; some have linked viral infections with Parkinson's disease (PD) based on results from cerebrospinal fluid analyses, and PD is speculated to impact the outcome of COVID-19 in patients negatively. In conclusion, the present paper reviewed the demographic, clinical, and treatment-associated information on de novo movement disorders in COVID-19 patients in detail; it also underlined the higher incidence of myoclonus and ataxia associated with COVID-19 than other movement disorders.

Early-onset bradykinetic rigid syndrome and reflex seizures in a child with PURA syndrome.

PURA syndrome is a distinct form of developmental encephalopathy, characterized by early-onset hypotonia, severe developmental delay, intellectual disability, epilepsy and respiratory and gastrointestinal disorders. We report a child with PURA syndrome, harbouring a previously described mutation, whose phenotype included two peculiar aspects: (1) hypokinetic-rigid syndrome, which was part of the clinical presentation from an early stage of the disease, and (2) reflex seizures, consisting of a series of spasms. We provide detailed clinical description and video recordings demonstrating both these aspects that are newly described in PURA syndrome. The early clinical features described here may therefore be included in the complex phenotype associated with PURA gene mutations and may help in the early diagnosis of patients. Furthermore, PURA syndrome should be considered in the differential diagnosis of early-onset bradykinetic rigid syndromes.

Pediatric Gaucher disease with intermediate type 2–3 phenotype associated with parkinsonian features and levodopa responsiveness

IntroductionGaucher disease (GD) is an autosomal recessive lysosomal storage disorder caused by a deficiency of acid β-glucosidase encoded by the GBA gene. In patients with GD, childhood onset parkinsonian features have been rarely described. MethodsTwin siblings with GD are described, including clinical follow-up and treatment response. Bone marrow, enzyme activity studies and genotyping were performed. ResultsBy age 9 months, symptoms at onset were thrombocytopenia and splenomegaly. By age 2, hypokinesia, bradykinesia and oculomotor apraxia were observed. By age 5 a complete rigid hypokinetic syndrome was stablished in both patients, including bradykinesia, tremor and rigidity. Treatment with imiglucerase, miglustat, ambroxol and levodopa were performed. Levodopa showed a good response with improvement in motor and non-motor skills. Foamy cells were found in the bone marrow study. Glucocerebrosidase activity was 28% and 26%. Sanger sequencing analysis identified a missense mutation and a complex allele (NP_000148: p.[(Asp448His)]; [(Leu422Profs*4)]) in compound heterozygosity in GBA gene. ConclusionsTwo siblings with neuronopathic GD with an intermediate form between type 2 and 3, with a systemic and neurological phenotype are described. The complex neurological picture included a hypokinetic-rigid and tremor syndrome that improved with levodopa treatment. These conditions together have not been previously described in pediatric GD. We suggest that in children with parkinsonian features, lysosomal storage disorders must be considered, and a levodopa trial must be performed. Moreover, this report give support to the finding that GBA and parkinsonian features share biological pathways and highlight the importance of lysosomal mechanisms in parkinsonism pathogenesis, what might have therapeutic implications.

Reader Response: Acute Hypokinetic-Rigid Syndrome After SARS-CoV-2 Infection.

We thank Dr. Méndez-Guerrero, et al. for their article on Acute hypokinetic-rigid syndrome after SARS-CoV-2 infection.1 Since 1917, when the first description of encephalitis lithargica 2 became available, the role of various viruses has been implicated in the etiopathogenesis of Parkinson's disease besides the environmental toxins and lifestyle, diet, pollution, etc.3 The interesting case report and details provided by Dr. Méndez-Guerrero, et al. are important in understanding the pathophysiology of hypokinetic rigid syndrome or Parkinsonian illnesses.

Editors' Note: Acute Hypokinetic-Rigid Syndrome After SARS-CoV-2 Infection.

In their case report, Dr. Méndez-Guerrero and colleagues add to the growing literature suggesting the neuroinvasive potential and neurologic sequelae of infection with the novel human coronavirus, SARS-CoV-2. Supported by dopamine transporter-SPECT imaging and negative testing for other known precipitants of Parkinsonism, this case exemplifies a rapidly improving postinfectious hypokinetic-rigid syndrome with associated generalized myoclonus and opsoclonus in a critically ill patient with coronavirus disease 2019 (COVID-19). The authors go on to imply that their case is reminiscent of the infamous encephalitis lethargica described by Constantin von Economo in 1917. Dr. Joseph Berger, neurovirologist and authority on von Economo's encephalitis, contests the relationship between SARS-CoV-2 and the clinical/radiologic observations made by the authors. Instead, Dr. Berger posits, the observations may be the consequence of hypoxic ischemic injury. In addition, the cases originally described by von Economo were observed years (not days) after an infectious illness. Dr. Shubhakaran recounts similar experiences with 2 patients who developed acute movement disorders after a viral prodrome; however, one was not tested for SARS-CoV-2 and the second tested negative by PCR. The authors maintain that their patient's oxygenation while intubated remained sufficient and would not have resulted in hypoxic ischemic injury. Furthermore, that the patient improved quickly and significantly would not be congruous with anoxic brain damage. The authors add credence to their argument by citing 2 related case reports of post-COVID-19 Parkinsonism that have been recently published. Nonetheless, we still need more clinical-pathological material to determine how neuroinvasive SARS-CoV-2 really is. In their case report, Dr. Méndez-Guerrero and colleagues add to the growing literature suggesting the neuroinvasive potential and neurologic sequelae of infection with the novel human coronavirus, SARS-CoV-2. Supported by dopamine transporter-SPECT imaging and negative testing for other known precipitants of Parkinsonism, this case exemplifies a rapidly improving postinfectious hypokinetic-rigid syndrome with associated generalized myoclonus and opsoclonus in a critically ill patient with coronavirus disease 2019 (COVID-19). The authors go on to imply that their case is reminiscent of the infamous encephalitis lethargica described by Constantin von Economo in 1917. Dr. Joseph Berger, neurovirologist and authority on von Economo's encephalitis, contests the relationship between SARS-CoV-2 and the clinical/radiologic observations made by the authors. Instead, Dr. Berger posits, the observations may be the consequence of hypoxic ischemic injury. In addition, the cases originally described by von Economo were observed years (not days) after an infectious illness. Dr. Shubhakaran recounts similar experiences with 2 patients who developed acute movement disorders after a viral prodrome; however, one was not tested for SARS-CoV-2 and the second tested negative by PCR. The authors maintain that their patient's oxygenation while intubated remained sufficient and would not have resulted in hypoxic ischemic injury. Furthermore, that the patient improved quickly and significantly would not be congruous with anoxic brain damage. The authors add credence to their argument by citing 2 related case reports of post-COVID-19 Parkinsonism that have been recently published. Nonetheless, we still need more clinical-pathological material to determine how neuroinvasive SARS-CoV-2 really is.

Reader Response: Acute Hypokinetic-Rigid Syndrome Following SARS-CoV-2 Infection.

The late astronomer Carl Sagan once said that “extraordinary claims require extraordinary evidence.”

Author Response: Acute Hypokinetic-Rigid Syndrome After SARS-CoV-2 Infection.

We thank Dr. Berger for the comment on our article1 but do not agree with the hypoxic-ischemic theory. First, the lowest Kirby index recorded in the ICU was 185 mm Hg while the patient was sedated and closely monitored. We recognize that, although significant, it was an isolated determination. Furthermore, it is well known that oxygen cerebral consumption is reduced during deep sedation.2

Parkinson's Disease and the COVID-19 Pandemic.

Studies focusing on the relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), coronavirus disease 2019 (COVID-19), and Parkinson’s disease (PD) have provided conflicting results. We review the literature to investigate: 1) Are PD patients at higher risk for contracting COVID-19 and are there specific contributing factors to that risk? 2) How does COVID-19 affect PD symptoms? 3) How does COVID-19 present in PD patients? 4) What are the outcomes in PD patients who contract COVID-19? 5) What is the impact of COVID-19 on PD care? 6) Does COVID-19 increase the risk of developing PD? A literature search was performed from 1979 to 2020 using the terms: ‘Parkinson’s disease’ and ‘parkinsonism’ combined with: ‘COVID-19’; ‘SARS-CoV-2’ and ‘coronavirus’. It does not appear that PD is a specific risk factor for COVID-19. There is evidence for direct/indirect effects of SARS-CoV-2 on motor/non-motor symptoms of PD. Although many PD patients present with typical COVID-19 symptoms, some present atypically with isolated worsening of parkinsonian symptoms, requiring increased anti-PD therapy and having worse outcomes. Mortality data on PD patients with COVID-19 is inconclusive (ranging from 5.2%to 100%). Patients with advanced PD appear to be particularly vulnerable. Single cases of acute hypokinetic-rigid syndrome have been described but no other convincing data has been reported. The rapidity with which COVID-19 has swept across the globe has favored the proliferation of studies which lack scientific rigor and the PD literature has not been immune. A coordinated effort is required to assimilate data and answer these questions in larger PD cohorts.

Idiopathic brain calcification in a patient with hereditary hemochromatosis

BackgroundDetection of brain-MRI T2/T2* gradient echo images (T2*GRE)-hypointensity can be compatible with iron accumulation and leads to a differential diagnosis work-up including neurodegeneration with brain iron accumulation (NBIA) and Wilson Disease. Idiopathic or secondary brain calcification can be also associated with neurological involvement and brain-MRI T2/T2*GRE-hypointensity. Hereditary hemochromatosis (HH), characterized by systemic iron loading, usually does not involve the CNS, and only sporadic cases of neurological abnormalities or brain-MRI T2/T2*GRE-hypointensity have been reported.Case presentationA 59-year-old man came to our observation after a diagnosis of HH carried out in another hospital 2 years before. First-level genetic test had revealed a homozygous HFE p.Cys282Tyr (C282Y) mutation compatible with the diagnosis of HFE-related HH, thus phlebotomy treatment was started. The patient had a history of metabolic syndrome, type-2 diabetes, autoimmune thyroiditis and severe chondrocalcinosis. Brain-MRI showed the presence of bilateral T2*GRE hypointensities within globus pallidus, substantia nigra, dentate nucleus and left pulvinar that were considered expression of cerebral siderosis. No neurological symptoms or family history of neurological disease were reported. Neurological examination revealed only mild right-sided hypokinetic-rigid syndrome. Vitamin D–PTH axis, measurements of serum ceruloplasmin and copper, and urinary copper were within the normal range. A brain computed tomography (CT) was performed to better characterize the suspected and unexplained brain iron accumulation. On the CT images, the hypointense regions in the brain MRI were hyperdense. DNA sequence analysis of genes associated with primary familial brain calcification and NBIA was negative.ConclusionsThis report highlights the importance of brain CT-scan in ambiguous cases of suspected cerebral siderosis, and suggests that HH patients with a severe phenotype, and likely associated with chondrocalcinosis, may display also brain calcifications. Further studies are needed to confirm this hypothesis. So far, we can speculate that iron and calcium homeostasis could be reciprocally connected within the basal ganglia.

Clinical and neuroimaging phenotypes of genetic parkinsonism from infancy to adolescence.

Genetic early-onset parkinsonism presenting from infancy to adolescence (≤21 years old) is a clinically diverse syndrome often combined with other hyperkinetic movement disorders, neurological and imaging abnormalities. The syndrome is genetically heterogeneous, with many causative genes already known. With the increased use of next-generation sequencing in clinical practice, there have been novel and unexpected insights into phenotype-genotype correlations and the discovery of new disease-causing genes. It is now recognized that mutations in a single gene can give rise to a broad phenotypic spectrum and that, conversely different genetic disorders can manifest with a similar phenotype. Accurate phenotypic characterization remains an essential step in interpreting genetic findings in undiagnosed patients. However, in the past decade, there has been a marked expansion in knowledge about the number of both disease-causing genes and phenotypic spectrum of early-onset cases. Detailed knowledge of genetic disorders and their clinical expression is required for rational planning of genetic and molecular testing, as well as correct interpretation of next-generation sequencing results. In this review we examine the relevant literature of genetic parkinsonism with ≤21 years onset, extracting data on associated movement disorders as well as other neurological and imaging features, to delineate syndromic patterns associated with early-onset parkinsonism. Excluding PRKN (parkin) mutations, >90% of the presenting phenotypes have a complex or atypical presentation, with dystonia, abnormal cognition, pyramidal signs, neuropsychiatric disorders, abnormal imaging and abnormal eye movements being the most common features. Furthermore, several imaging features and extraneurological manifestations are relatively specific for certain disorders and are important diagnostic clues. From the currently available literature, the most commonly implicated causes of early-onset parkinsonism have been elucidated but diagnosis is still challenging in many cases. Mutations in ∼70 different genes have been associated with early-onset parkinsonism or may feature parkinsonism as part of their phenotypic spectrum. Most of the cases are caused by recessively inherited mutations, followed by dominant and X-linked mutations, and rarely by mitochondrially inherited mutations. In infantile-onset parkinsonism, the phenotype of hypokinetic-rigid syndrome is most commonly caused by disorders of monoamine synthesis. In childhood and juvenile-onset cases, common genotypes include PRKN, HTT, ATP13A2, ATP1A3, FBX07, PINK1 and PLA2G6 mutations. Moreover, Wilson's disease and mutations in the manganese transporter are potentially treatable conditions and should always be considered in the differential diagnosis in any patient with early-onset parkinsonism.

Double Hit Theory for the Development of Vascular Parkinsonism

Introduction: Identify the non-decoded network in Vascular Parkinsonism (VasP). Objective: To determine what pattern of stroke lesions is responsible for VasP, as compared to those patients who had stroke, gait and balance problems, but absence of a hypokinetic rigid syndrome also called Vascular Pseudo Parkinsonism-V PSeuP. Materials and Methods: Design: prospective cohort study. Participants were consecutively screened for parkinsonian symptoms during a year as according to our previous study. Validated questionnaire (Tanner Questionnaire-TQ) was used, and a new scale operationalizing the criteria for VasP (FMAS score). All participants in the original study had a clinical exam to identify if presence of a hypokinetic rigid syndrome. Lesion patterns were analyzed. Setting: tertiary care stroke prevention clinic at the University of Alberta Hospital. Participants: Eligible participants attained a score of ≥ 4 on the TQ, high risk for parkinsonism. Four groups were considered: V PseuP, VasP (onset of parkinsonism within a year of the stroke -FMAS score of 4), Pseudo Vascular Parkinsonism-PseuVP (hypokinetic rigid syndrome not related to stroke), and Pseudo Vascular Pseudo Parkinsonism-PseuV PseuP (no stroke and no extrapyramidal syndrome), but with gait and balance problems. Baseline demographic information and clinical characteristics were recorded including vascular risk factors, and stroke subtype. All participants had a Holter, CT head and/or brain MRI, and CTA. Medications that produce drug-induced-parkinsonism were recorded for every participant. The primary outcome was to find the pattern of anatomical lesions particularly involved in the VasP subgroup considering the Basal Ganglia Motor Output Circuit-BGMO, the Thalamo Cortical Drive Loop-TCD and connections to frontal cortex. Results: 240 consecutive participants were screened during 12 months. We found 46 patients with potential Parkinsonism (TQ>4). VPseuP was found in 25/46 (54%), VasP in 8/46 (17%), PseuVP in 7/46 (15%), and PseuV PseuP in 6/46 (14%). VasP were older (p<0.0007) and had a higher risk for cardio embolism due to atrial fibrillation (p=0.02, odd ratio 6.6 CI 95% (1.2 – 35.2)). Neuro images showed that only the pattern involving the BGMO and frontal cortex was significantly associated to the group of VasP (X2 Fisher exact test p<0.0005 Odds ratio 32 CI 95% (9.6-108)); whereas the pattern TCD was not significantly different between the groups (X2 Fisher exact test p=0.828 Odds ratio 1.2 CI 95% (0.5-2.8)). Discussion and Conclusion: A two strategic location hit within the BGMO circuit and frontal cortex is required, so a phenotype of VasP may occur.

Neurotransmitter trafficking defect in a patient with clathrin (CLTC) variation presenting with intellectual disability and early-onset parkinsonism

IntroductionClathrins play a key role in endocytosis, recycling, and trafficking as well as the generation of presynaptic vesicles. We report a new clinical condition associated with a de novo variant in the CLTC gene, which encodes the clathrin heavy polypeptide. Case reportThis 30-year-old woman presented with a developmental disorder during childhood that progressed to mild cognitive decline in late childhood and relapsing-remitting hypokinetic-rigid syndrome with severe achalasia, weight loss, and mood disorder in adulthood. 123I-Ioflupane SPECT was normal. Blood phenylalanine was slightly increased and PAH sequencing revealed compound heterozygosity for two variants, p.[Asp151Glu]:[Thr380Met]. CSF examination unexpectedly detected a remarkable reduction of homovanillic, 5-hydroxyindolacetic, and 5-methylthetrahydrofolic acids, which could not be ascribed to any alteration of tetrahydrobiopterin and related biogenic amine pathways. MethodsTrio-based exome sequencing was performed. ResultA de novo missense variant (c.2669C > T/p.Pro890Leu) was detected in CLTC. Treatment with biogenic amine precursors was ineffective, while the inhibitor of MAO-A selegiline resulted in persistent clinical improvement. ConclusionsWe suggest CLTC defect as a new disorder of biogenic amine trafficking, resulting in neurodevelopmental derangement and movement disorder. Neurotransmitter depletion in CSF may be a biomarker of this disease, and selegiline a possible treatment option.

A Compound Heterozygous for Novel Mutations in tyrosine Hydroxylasegene with Hypo kinetic-Rigid Syndrome with Dystonia

A Compound Heterozygous for Novel Mutations in tyrosine Hydroxylasegene with Hypo kinetic-Rigid Syndrome with Dystonia

Cerebrospinal Fluid Monoamine Metabolite Analysis in Pediatric Movement Disorders.

Abnormal concentrations of dopamine and serotonin metabolites in the cerebrospinal fluid is the diagnostic hallmark of a group of treatable conditions known as the monoamine neurotransmitter disorders. We assessed cerebrospinal fluid dopamine and serotonin metabolite concentrations in a series of 69 patients affected by movement disorders of unknown etiology. Abnormal results were disclosed in 13/69 subjects (19%). Both primary and secondary monoamine neurotransmitter disorders were observed. The clinical presentation of both forms was hypokinetic-rigid syndrome or dystonia. L-Dopa treatment resulted in significant improvement of the clinical picture in the majority of primary neurotransmitter disorders. Eight patients presented a secondary neurotransmitter disorder. One suffered from a GM2 gangliosidosis and one from infantile bilateral striatal necrosis. Etiologic diagnoses were not established in the others. L-Dopa was started in four patients, leading to a significant improvement of hypokinesia in the patient suffering from GM2 gangliosidosis and a slight improvement in 3 unclassified patients.

Parkinsonism and inborn errors of metabolism.

Parkinsonism is a frequent neurological syndrome in adulthood but is very rare in childhood. Early forms of Parkinsonism have many distinctive features as compared to Parkinsonism in adults. In fact, rather than Parkinsonism, the general concept "hypokinetic-rigid syndrome" (HRS) is more accurate in children. In general, the terms "dystonia-parkinsonism", "parkinsonism-plus", or "parkinsonism-like" are preferred to designate these forms of paediatric HRS. Inborn errors of metabolism (IEM) constitute an important group amongst the genetic causes of Parkinsonism at any age. The main IEM causing Parkinsonism are metal-storage diseases, neurotransmitter defects, lysosomal storage disorders and energy metabolism defects. IEM should not be neglected as many of them represent treatable causes of Parkinsonism. Here we review IEMs causing this neurological syndrome and propose diagnostic approaches depending on the age of onset and the associated clinical and neuroimaging features.

Parkinsonian syndrome and ataxia as a presenting finding of acquired hepatocerebral degeneration

The term "acquired hepatocerebral degeneration" (AHD) was coined to describe clinical entity distinct from genetically defined Wilson's disease. AHD is chronic neurological disorder, characterized by extrapyramidal and neuropsychiatric symptoms accompanied with advanced liver disease with portosystemic shunts. In majority of AHD cases, extrapyramidal symptoms appear in the presence of known liver disease. Here we present a patient with subacute onset of bilateral, asymmetric, hypokinetic-rigid syndrome and ataxia as initial presentation of liver cirrhosis. Manganese toxicity have major role in AHD pathogenesis. Failure of liver detoxification and presence of portosystemic shunting enables neurotoxic substance of manganese to avoid hepatic metabolism and to enter and accumulate in central nervous system. Predilection brain regions for manganese deposits are globus pallidum (GP) and substantia nigra (SN). Characteristic MRI findings of bilateral, symmetrical hyperintensities of GP and SN on T1-weighted sequences supported the diagnosis of AHD in our patient. In addition, increased T2 signal in dendate nuclei seen in our patient is rare radiological finding. So far, no consensus guidelines regarding medical treatment of AHD exist. We initiated low-dose levodopa treatment, but failed to provide beneficial effect. In conclusion, AHD is distinct clinical entity that should be included in differential diagnosis of both typical and atypical parkinsonian syndromes. Furthermore, our case highlights the importance of performing MRI in patients with atypical parkinsonism.

Narcolepsy with cataplexy and parkinson’s disease – A case report

Narcolepsy with cataplexy (NC) is a sporadic neurological disease with prevalence 0.02–0.067% and it is caused by the loss of hypocretin neurons in lateral hypothalamus. NC is associated with HLA DQB1*06:02 allele. Parkinson‘s disease (PD) is a degenerative disorder manifested by hypokinetic-rigid syndrome, caused by degeneration of dopamine-producing cells in the substantia nigra pars compacta. The prevalence of PD is 0.1–0.2%. In addition to cardinal motor symptoms (akinesia, rigidity, tremor and postural instability), autonomic and sensory disturbances as well as cognitive, behavioral and sleep problems can occur during the disease progression. This is a case report presentation. An 86-year-old Caucasian woman suffering from NC was diagnosed at our department in 1980s. Daytime polysomnography (PSG) was performed, demonstrating typical SOREMPs. The patient was treated by phenmetrazin and imipramin or clomipramin. In 1995 the patient was retired and her narcoleptic symptoms became less prominent. The patient stopped the therapy and dropped out from the contact with our department. Hypokinetic-rigid syndrome with symmetric rigidity and akinesia in upper extremities and mild gait difficulty with instability was diagnosed when the patient was 83 year old. Patient’s symptoms stabilized after pramipexol 0.7 mg bid initiation. At the age of 85, the patient reported disturbing hypersomnia and frequent falls, which led to reevaluation in our department. Patient reported frequent daytime sleep attacks with variable duration. The sleepiness was present in rest as well as during social activities. The falls, mostly backwards were not caused by emotions nor associated with decreased muscle tone. Sometimes these were preceded by lightheadedness and pre-syncopal syndromes, but mostly were related to gait instability. Patient did not report hypnagogic hallucinations or sleep paralysis. Night PSG revealed frequent PLMS, severe sleep apnea (AHI 43), MSLT confirmed narcolepsy (short sleep latency and 2 SOREMPs), HLA typing showed haplotype HLA DQB1*06:02. Clinical examination showed typical parkinson’s syndrome (motor subscale of UPDRS 28) with good response to dopaminergic treatment and the diagnosis of idiopathic PD was established. We report this case because the co-occurrence of NC and PD is very rare according to the literature. IGA MZ ÈR: NT 13238–4/2012.