Brian Magennis

Pallidopontonigral degeneration: a deceptive familial tauopathy.

Pallidopontonigral degeneration (PPND) is 1 of the frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) disorders. It manifests with various neurological and neuropsychiatric features. Parkinsonism is almost invariably present at the outset, hence early PPND may readily be misdiagnosed as idiopathic Parkinson’s disease (PD) or progressive supranuclear palsy (PSP). Early parkinsonism distinguishes PPND from other FTDP-17 syndromes, which are characterized by early personality change and frontal lobe dysfunction.

Failure of Sequential Pallidal and Motor Thalamus DBS for Rapid-Onset Dystonia-Parkinsonism (DYT12)

Rapid-onset dystonia-parkinsonism (DYT12) is an autosomal dominant combined dystonia associated with mutations of the ATP1A3 gene. Onset is precipitated abruptly by physical/psychological stressors. Dystonia displays a rostrocaudal distribution with prominent orofacial and upper limb involvement, with symptoms remaining refractory to dopaminomimetic or GABA-mimetic agents. It is also the preeminent movement disorder in DYT12, with little parkinsonism, including bradykinesia (possibly reflecting dystonic slowing without decrement). We describe the response to sequential deep brain stimulation (DBS) of the globus pallidus internus (GPI) and, subsequently, the thalamic zona incerta and nucleus ventralis oralis posterior (VOP) in a patient from the Irish DYT12, which was described in detail by Pittock and colleagues. The 8-year-old patient, while playing in a playground, fell to the ground after hanging upside-down. After several minutes she began to whisper. Over the next fortnight, her speech deteriorated, and she subsequently became anarthric. She developed significant upper limb dystonia and dystonic posturing of the left foot. Slow rapidly alternating movements and facial dystonia were noted. MRI brain, neurometabolic bloods, and CSF were normal. Genetic analysis identified a C1838T point mutation in exon 14 of the ATP1A3 gene, co-segregating with disease phenotype in the family. There was no response to pharmacotherapy with levodopa, benzodiazepines, or acetazolamide. Bilateral GPI DBS was performed. Postoperatively, serial assessments identified objective deterioration in communication and feeding; verbal communication was eventually lost and she developed jaw opening dystonia. With optimization of her DBS parameters, she had fluctuating improvement of left arm function. Paradoxically, despite worsening oromandibular dystonia, it was easier to bring food to her mouth. Over time, it became apparent that DBS adjustments to improve orofacial symptoms were consistently coupled with deterioration in upper limb dystonia. Having failed to optimize GPI stimulation, she had further surgery to target the nucleus ventralis oralis posterior (VOP; a pallidal receiving area) and zona incerta (ZI). The previous pallidal system was removed. Postoperative imaging confirmed satisfactory lead placement (Fig. 1). After initial stimulation, she noticed increased difficulty swallowing, which improved with down-titration. There has been little improvement in either the orofacial or upper limb dystonia (Video S1). DYT12 remains a formidable disorder to treat and lack of response to medical therapy makes DBS appealing as a therapeutic option, however evidence is limited. Given the favorable outcomes seen in other primary dystonias, including DYT1 or similarly combined dystonias, including Lubag, it is disappointing that DBS of GPI or motor thalamus (VOP and ZI) has not resulted in significant improvements in this patient. One previous report of DBS in genetically confirmed DYT12 (GPI satisfactorily targeted) showed a reduction in dystonia severity of “borderline” clinical significance. Previous reports of pallidal +/STN-DBS in non-genetically defined, rapid-onset dystonic, and parkinsonian syndromes did not demonstrate benefit. We describe the second case of GPI DBS and the first case of VOP/ZI DBS in DYT12. There was no significant

Reversible Corticobasal Syndrome due to Coeliac Disease: Reversible Cbs Due To Coeliac Disease

Coeliac disease (CD) can present with cerebellar ataxia, peripheral neuropathy, gluten encephalopathy, epilepsy with occipital calcifications, and (rarely) ataxia with cortical myoclonus. Myoclonic ataxia is often associated with refractory CD. The myoclonus is cortical and often progressive. We describe a woman with coeliac disease, myoclonic ataxia, and corticobasal syndrome (CBS) with alien limb phenomenon that resolved with immunosuppression.

A Wolf in Sheep’s Clothing: An “Alien Leg” in Corticobasal Syndrome

Background Alien limb phenomenon occurs in 50–60% of patients with corticobasal syndrome (CBS) and usually presents with an “alien hand” phenomenon. The “alien foot” presentation is rarer and may be misdiagnosed, as foot involvement can lead to erroneous localization of the clinical problem to the knee, hip, or back. Subsequently misdiagnoses such as myelopathy, radiculopathy, functional disorder, stiff leg syndrome, neuromyotonia, and painful leg moving toes syndrome may occur. Case report We describe two patients with alien foot symptoms that resulted in multiple opinions from different specialists, multiple diagnostic and therapeutic procedures, and delayed diagnosis. Eventually a diagnosis of CBS was made in both. Alien foot symptoms may be more common than initially thought and can result in a delayed diagnosis of CBS. Conclusion The inclusion of this clinical finding in recently proposed diagnostic criteria highlights the need for increased clinical awareness.

CP2 A portrait of the artist as a young woman with parkinsonism: a clinical and videographic record of pallidopontonigral degeneration

A 36-year-old female artist presented with bradykinesia of left arm and left leg, slight tremor, decreased voice volume, loss of facial expression and bradyphrenia. Her father had developed parkinsonism aged 36 and died aged 52. Examination revealed hypomimia, hypophonia, square wave jerks and subtle left-sided bradykinesia. Cognitive assessment was normal. Following multiple neurological opinions, she was diagnosed with familial idiopathic Parkinsons disease (PD). Initial treatment with l-dopa was of limited benefit and caused orofacial dystonia. She became progressively more bradykinetic, fell frequently, and apraxia of eyelid opening, aphonia and dysphagia ensued. T2-weighted MRI revealed high signal in the mesiotemporal regions bilaterally. Genetic studies detected an N279K mutation of the microtubule-associated protein tau (MAPT) gene on chromosome 17, prompting a diagnosis of pallidopontonigral degeneration (PPND). PPND was first described in 1992 as a rapidly progressive autosomal dominant syndrome of parkinsonism and dementia. It falls within the frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) spectrum of disorders. PPND mimics idiopathic PD early in the disease course and can be associated with near-normal cognition as in this patient. Recent studies suggest a potential biomarker role for MRI. This case, illustrated with sequential videos, delineates the natural history of this entity.