Difficult case of a rare form of familial Alzheimer's disease with PSEN1 P117L mutation.

Less than 10% of Alzheimer's disease (AD) cases are familial. Presenilin-1 (PSEN1) mutations are the most frequent aetiology and may be associated to atypical neurological manifestations. We report the case of a 27-year-old right-handed man, ensuing with mild cognitive impairment, motor discoordination and axial myoclonus after a parachute accident. At age 32 he was referred to our neurology clinic, presenting cognitive impairment, cerebellar syndrome, axial myoclonus and hypomimia, without other signs of parkinsonism. Because of absence of family history, he was worked up along the line of spinal ataxic disorders. Later, he developed pseudobulbar affect, cognitive deterioration, right upper limb paresis and spastic paraparesis. Subsequent investigation identified a PSEN1 P117L mutation and the diagnosis of autosomal dominant AD was made. This case illustrates the diagnostic challenge imposed by atypical presentation of de novo PSEN1 mutation, leading to unnecessary investigation. Genetic study might be essential for defining the diagnosis.

Parkinson's Disease and development of levodopa induced motor complications: Influence of baseline features and first medical approach.

BACKGROUND: The introduction of levodopa in clinical practice represents a hallmark in the treatment of the neurodegenerative disease, Parkinson's Disease. However, levodopa induced motor complications, namely dyskinesias and motor fluctuations, develop in the majority of Parkinson's Disease patients. OBJECTIVE: to identify which Parkinson's Disease's, patient's and therapeutics' initial features are more associated with dyskinesias or motor fluctuations development. METHODS: Patients with diagnosed Parkinson's Disease attending neurology outpatient clinic at Centro Hospitalar São João were selected. For this observational study, data was retrospectively collected from patient's clinical records. A survival analysis model with univariate and multivariate regression analysis was used. RESULTS: 87 patients with a mean of 72 ± 9.7 years were included. After a median follow-up of 6 (range 1-17) years, 35.6% patients developed dyskinesias; and with a median of 5 (range 1-16) years, 32.2% developed motor fluctuations. After multivariate analysis, the akinesia/rigidity subtype was found to have a higher risk of dyskinesias and motor fluctuations development. Age of onset ≤50 years was associated with motor fluctuations development. CONCLUSION: In conclusion, our results suggest that Parkinson's Disease patients' initial characteristics, such as subtype or age of onset, are independently associated with the development of motor complications.

Isolated III cranial nerve palsy: a Hodgkin's lymphoma?

A 69-year-old woman developed ptosis and diplopia due to an isolated pupil-involving left oculomotor nerve palsy. General examination was unremarkable. Initial workup showed a mild increase in cerebrospinal fluid proteins. Imaging studies were remarkable for a left oculomotor nerve enhancement in brain MRI and hyperfixation along the nerve's pathway in full body single-photon emission CT. Assuming the possible diagnosis of neurosarcoidosis, the patient was started on high-dose methylprednisolone. Three months later she developed pancytopenia. A bone marrow biopsy was performed and histopathology revealed infiltration by Hodgkin's lymphoma. Adriamycin, bleomycin, vinblastine, dacarbazine protocol chemotherapy was started and full haematological remission obtained after four cycles, despite mild oculomotor nerve palsy persisted. Isolated oculomotor palsy as the first presenting manifestation of a lymphoma is rare and alternative differential diagnosis must be considered in the absence of other lymphoma manifestations. In this case as with many rare initial manifestations of common diseases watchful waiting was crucial to the correct diagnosis and treatment strategy.

Reversible parkinsonism due to a large intracranial tumour.

A 77-year-old woman presented with progressively worsening apathy, depression, urinary incontinence and slowness of movement for the past 1 year. Asymmetric akinetic-rigid parkinsonism and mild left-sided hyper-reflexia were seen on examination. No ocular movement impairment, cerebellar or sensory signs were noticed. Routine laboratory testing was normal. Brain imaging revealed a large frontal tumour which was subsequently excised and pathologically confirmed as a meningioma. Marked clinical improvement was documented 3 months after surgery, and persistent clinical and imaging remission have been confirmed annually for the following 3 years. There have been some reports of parkinsonism associated with intracranial tumours. Although this is probably an uncommon situation, it is potentially treatable, and symptoms might even remit completely following successful management. Parkinson's disease is a common cause of parkinsonism, but alternative aetiologies should be suspected whenever atypical findings are demonstrated by clinical history or examination.

Stretching the limbs? Tonic spasms in multiple sclerosis.

A 23-year-old man with a clinically isolated syndrome (right optic neuritis) diagnosed 6 months before, presented with recurrent, brief, painful, stereotyped, involuntary posturing movements of the left upper limb. The neurological examination was otherwise unremarkable (except for right optic atrophy). Intravenous methylprednisolone was initiated; the paroxysms persisted and worsened 7 days later, as the left lower limb and hemiface became affected. A video-EEG showed no epileptiform activity despite the movements. Brain MRI revealed new lesions affecting the right pyramidal tract, contralateral to the clinical manifestations. Valproate was prescribed and the paroxysms were completely resolved 5 days later. Tonic spasms are classically, although infrequently, seen in multiple sclerosis, and may clinically resemble primary paroxysmal dyskinesias or even focal motor epileptic seizures.

The role of breast MRI in the investigation of anti-Yo positive paraneoplastic cerebellar degeneration.

Paraneoplastic neurological syndromes are a group of rare and heterogeneous disorders complicating cancer through immune-mediated mechanisms. They typically arise before the diagnosis of malignancy, thus constituting its first clinical manifestation. A thorough search for the underlying tumour is necessary, as adequate tumour management is essential for both neurological prognosis and overall survival. The authors present the case of a 43 year-old woman who presented with a subacute cerebellar syndrome associated with the paraneoplastic anti-Yo antibody. Although paraneoplastic aetiology was immediately suspected, the diagnosis of the underlying tumour was not straightforward, as is often the case. This case report highlights the importance of directing tumour search for the most probable anatomic locations, according to patient demographics and risk factors as well as the type of onconeural antibodies present, and also the need to use the most sensitive diagnostic modalities appropriate for each target organ.