Joana Damásio

Systemic Lupus Erythematosus, Progressive Multifocal Leukoencephalopathy, and T-CD4+ Lymphopenia

Progressive multifocal leukoencephalopathy (PML) is a rare opportunistic infection caused by the reactivation of JC virus and occurs in patients with severe primary or secondary immunosuppression. Recently, PML is becoming relevant in autoimmune disorders, particularly in patients treated with biologic agents. However, systemic lupus erythematosus (SLE) appears to be associated with susceptibility to PML that cannot be entirely explained by the immunosuppressive therapy. The authors present two patients with the diagnosis of SLE and PML: One had a heavy immunosuppressive therapy history, and the other had never experienced biologic or cytotoxic therapeutics. Both patients had a profound T-CD4+ lymphopenia during their clinical history. These two cases emphasize the importance of CD4+ lymphopenia in SLE patients with and without immunosuppressors regarding opportunistic infections.

Cerebellar Ataxia, Hemiplegic Migraine, and Related Phenotypes Due to a CACNA1A Missense Mutation 12-Year Follow-up of a Large Portuguese Family

OBJECTIVE To document and discuss the broad phenotypic variability in a Portuguese family with cerebellar ataxia, hemiplegic migraine, and related syndromes caused by missense mutation c.1748 (p.R583Q) in the CACNA1A gene. DESIGN Observational 12-year follow-up study. SETTING Community and hospital care. PATIENTS Sixteen patients in a 4-generation family were identified in 1998 in a population-based survey. The follow-up revealed 28 patients (25 of whom were observed) and 32 unaffected relatives with an a priori risk of 50%. RESULTS Four major phenotypes (migraine with multiple auras, transient focal neurological deficits without headache, coma triggered by minor head trauma, and slowly progressive cerebellar ataxia) were present in various combinations. The initial manifestation was ataxia in 16 patients and a transient episode in 12 patients. Eighteen patients did not have migraine, and 11 showed only ataxia. The c.1748 (p.R583Q) mutation in CACNA1A was confirmed in all 23 of the patients who were tested but was not found in any of the 27 adult relatives. The CACNA1A CAG repeat expansion was excluded. CONCLUSIONS A unique missense mutation in the CACNA1A gene, which exhibits a very high penetrance and expressivity, may present a phenotypic spectrum that is broader than current descriptions. Single-gene disorders can behave as complex traits, which reinforces the importance of genetic modifiers in the tightly regulated function of P/Q-type calcium channels. The clinical spectrum of missense mutation CACNA1A -related disorders is much broader than strictly familial hemiplegic migraine.

Abnormal Olfaction in Parkinson’s Disease Is Related to Faster Disease Progression

Introduction. A possible association between olfactory dysfunction and Parkinsons disease (PD) severity has been a topic of contention for the past 40 years. Conflicting reports may be partially explained by procedural differences in olfactory assessment and motor symptom evaluation. Methods. One hundred and sixty-six nondemented PD patients performed the Brief-Smell Identification Test and test scores below the estimated 20th percentile as a function of sex, age, and education (i.e., 80% specificity) were considered demographically abnormal. Patients underwent motor examination after 12 h without antiparkinsonian medication. Results. Eighty-two percent of PD patients had abnormal olfaction. Abnormal performance on the Brief-Smell Identification Test was associated with higher disease severity (i.e., Hoehn and Yahr, Unified Parkinsons Disease Rating Scale-III, Freezing of Gait questionnaire, and levodopa equivalent dose), even when disease duration was taken into account. Conclusions. Abnormal olfaction in PD is associated with increased severity and faster disease progression.

Appendectomy may delay Parkinson's disease Onset

Alpha‐synuclein (α‐Syn) is particularly abundant in the vermiform appendix, which makes this structure an anatomical candidate for the initiation of Parkinsons disease (PD) pathology. We hypothesized that history of appendectomy might affect PD clinical onset.

Familial hemiplegic migraine due to L263V SCN1A mutation: Discordance for epilepsy between two kindreds from Douro Valley

Background SCN1A is the most relevant gene in epilepsy. Only seven SCN1A mutations have been identified in 10 familial hemiplegic migraine (FHM) kindreds worldwide. Cases and kindreds In 2009, we presented a kindred with FHM due to the L263V SCN1A mutation. In the current study, we report a novel FHM3 kindred from the same village. The first family exhibited the co-occurrence of FHM and epilepsy. No case of epilepsy was observed in the new kindred. An L263V mutation was found in all patients, and the haplotype analysis supports a unique mutational event. Comments Despite its bioelectric activity, the SCN1A L263V mutation most likely requires a combination of several endogenous or environmental induction stimuli to attain an epileptogenic threshold.

Adult‐Onset Primary Dystonic Tics: A Different Entity?

Based on their phenomenology, tics can be classified as clonic, dystonic, and tonic. Although tic syndromes are considered to be childhood disorders, there are reports on (clonic) tics developing late in life. Literature on dystonic tics is sparse, and it is unclear whether adult‐onset dystonic tics are part of the same disorder spectrum that includes Tourettes syndrome or represent a discrete entity. We describe here 11 patients with adult‐onset primary dystonic tics. Ten patients (90.1%) were males. Mean age at onset was 42.2 ± 14.9 years. More than 60% had both motor clonic and dystonic tics. Dystonic tics most frequently involved the cranial‐cervical region and the shoulders and, less frequently, the limbs. Psychiatric comorbidities were present in 5 patients. Family history for any movement disorder or for psychiatric disorders was present in 2 cases. One patient showed a sensory geste, which allowed him to partially control his tics, whereas another developed overt dystonia 3 years after his first assessment. The hyperkinesias exhibited by these patients were likely consistent with tics. However, other clinical features would allow us to argue that adult‐onset dystonic tics may represent a discrete entity, which is intermediate between tics and dystonia.

Migraine-Induced Epistaxis and Sporadic Hemiplegic Migraine: Unusual Features in the Same Patient

Background: Since the mid-19th century, epistaxis and migraine have been occasionally associated with each other. Nevertheless, we found only two cases in the contemporary medical literature. Sporadic hemiplegic migraine is a subtype of migraine with reversible motor deficits, without similar episodes in relatives. Case: We describe a 47-year-old male with a history of migraine with a scintillating scotoma starting at the age of 20. In some of the episodes, he developed epistaxis in the resolution phase of migraine. At the age of 35, he experienced a visual aura followed by transient aphasia, left crural weakness and headache. Contralateral similar episodes occurred in the subsequent months. Neurological examination and MRI were normal. Mutations in CACNA1A, ATP1A2, SCN1A and NOTCH3 were excluded. Discussion: Three distinct aspects deserve our consideration. This is the first report of migraine-induced epistaxis involving aura; the scarcity of similar reports may be due to the lack of a guided anamnesis. The complex aura presented had a peculiar topography, inconsistent with the classical analytical neurological semiology. This may suggest that the spreading depression affects the brain bilaterally but in an uneven and elective manner. Lastly, the present report conveys that the late appearance of complex auras requires improbable interactions between environmental and endogenous conditions in individuals with a genetic predisposition.

A coincidental case of young-onset Parkinson disease and multiple sclerosis.

BACKGROUND Parkinsonism in patients with multiple sclerosis is rare. Some patients have 2 coincidental diseases, whereas others have a Parkinsonian syndrome symptomatic to demyelinating lesions. CASE REPORT We describe a 42-year-old female patient who developed left akinetic-rigid Parkinsonian syndrome at the age of 38 years. Brain magnetic resonance imaging revealed multiple white matter hyperintense T2-weighted lesions. DaTSCAN revealed reduced uptake of dopamine transporter in the right striatum. Intravenous corticosteroids were inefficacious. She had major clinical improvement with levodopa and 6 months later developed peak-dose dyskinesias. At the age of 41 years, she presented with a brainstem attack, with complete symptom resolution after intravenous corticosteroids. Subsequent brain magnetic resonance imagings disclosed new inflammatory lesions. Immunomodulatory treatment was started with β-interferon. COMMENTS In this patient, the presence of an asymmetrical Parkinsonian syndrome, with good response to levodopa, peak-dose dyskinesias, and abnormal DaTSCAN, supports the diagnosis of young-onset Parkinson disease. The multiple sclerosis diagnosis was established based on clinical evidence of time and space dissemination of demyelinating lesions.

Survival, mortality, causes and places of death in a European Huntington's disease prospective cohort

Huntingtons disease (HD) is a rare and fatal inherited genetic disorder characterized by progressive motor, cognitive, and behavioral impairment. It leads to premature death, but data regarding advanced‐stage disease are scarce. We sought to determine HD‐associated survival, mortality, and causes and places of death.

Freezing of gait--first motor manifestation in late infantile variant neuronal ceroid lipofuscinosis.

Freezing of gait is generally seen in adults with degenerative or vascular parkinsonism [1], being very uncommon in infants or children. Neuronal ceroid lipofuscinoses (NCL) comprise a large group of neurodegenerative lysosomal disorders clinically characterized by progressive loss of vision, psychomotor deterioration, epilepsy and early death [2]. Historically, classification has been based on age of onset, ultrastructural morphology of the storage material showed by electron microscopy and genetic defect [3]. In CLN6 disease, late infantile variant, the onset is between18 months to 8 years [2]. The most important clinical features are seizures andmotor deterioration, followed by myoclonus, speech impairment, ataxia and mental regression [2]. Here we present a boy with CLN6 disease and freezing as first motor symptom. The 8 year-old boy of Portuguese descent was born of nonconsanguineous parents, after unremarkable gestation and delivery. He had normal developmental milestones apart from a moderate delay in expressive language acquisition. By the age of 3 years he presented multiple generalized tonic clonic, myoclonic and atypical absences seizures. His epilepsy was refractory to treatment, despite adequate trials of multiple antiepileptic drugs. At 4 years he developed freezing of gait, in the absence of other parkinsonian signs. Freezing would appear when starting to walk, going through narrow passages or walking in open spaces (video segment one). All by himself he learned strategies to overcome freezing, like flexing his thigh when starting to walk (video segment one). He presented rapid motor deterioration and, a month later, was unable to walk without help. By that time he had a complex gait disorder, characterized by a mixture of freezing, apraxia, ataxia and postural instability (video segment two). Simultaneously visual impairment was detected. His condition declined over the years with language regression, blindness and appearance of pyramidal signs (spasticity, extensor plantar response) (video segment three). For a year he has his seizures controlled. He is currently bedridden, has almost no communication skills, and is being fed through a percutaneous gastrostomy.