Lubag Dystonia Parkinsonism
Patient #33 is a young Filipino male who presented with typical features of Parkinsonism (bradykinesia, cogwheel rigidity, resting tremor, and postural instability) associated with dystonia of the feet and jaw. These findings placed the responsible lesion in the subcortex, affecting the nigrostriatal pathways. As has been discussed in previous cases, the differential diagnosis of Parkinsonism is broad, encompassing many possible etiologies. In a patient of this age, one must especially consider drug exposure (anti-psychotics, anti-emetics, etc.), Wilson's disease, Huntington's chorea, neuroacanthocytosis, multi-system atrophy (striatonigral degeneration, olivopontocerebellar atrophy, Shy-Drager syndrome), PSP, and various hederodegenerative causes of Parkinsonism. Most secondary causes of Parkinsonism (other than possible drug exposure) are unlikely in this case. There was no preceding history of encephalitis or other infection, no history of significant trauma, and no evidence to suggest a paraneoplastic, or structural cause of this patient's condition.
Wilson's disease must be considered in the differential diagnosis of any movement disorder in the young, since it is not only treatable, but also the source of significant morbidity and mortality if not diagnosed early. Neurological symptoms are present in over half of patients on presentation, and may precede hepatic or psychiatric complaints. Dystonia, tremor, parkinsonism, and chorea commonly occur. However, the lack of Kaiser-Fleisher rings essentially eliminates Wilson's disease as a possibility, since they are present in almost 100% of cases with neurological manifestations. A normal ceruloplasmin level was found, as well. One case has been published in the literature, however, of Wilson's disease with neurological manifestations lacking Kaiser-Fleisher rings.
Neuroacanthocytosis is an unusual but commonly overlooked cause of Parkinsonism in the young. Onset of symptoms is in the third or forth decade. Symptoms include orofacial dyskinesias, chorea, dystonia, parkinsonism, cognitive changes, and a predominantly motor neuropathy. Patients with this disease have prominent acanthocytes on peripheral blood smear (at least 10% of RBCs). A motor neuropathy is usually found on nerve conduction velocities. Imaging studies may reveal marked caudate atrophy, especially in late cases. All of the above diagnostic features were absent in this patient. In addition, no acanthocytes were identified on peripheral smear.
Levodopa-responsive dystonia, characterized by diurnal variation with dystonia affecting the legs earlier and more severely than the arms, could present in a fashion similar to this. However, the average age of onset is six years, with a 2:1 ratio of females to males. Occurrence with Parkinsonism would not be expected. Although this diagnosis seemed unlikely, a trial of Sinemet was attemted, with no change in his symptoms.
Several hederodegenerative conditions present in the young patient with Parkinsonism. Among these conditions, Huntington's chorea may present with Parkinsonism and dystonia, especially in young patients, but there was no clear family history of this condition. Most patients with the rigid form of Huntington's disease have the onset of the process before the age of 20, and virtually all demonstrate some adventitious movements in addition to the bradykinesia. There was no evidence on neuroimaging to suggest Hallervorden-Spatz disease and onset at this age would be atypical. The slow progression argues against prion disease, and there was no suggestive laboratory evaluation (e.g. EEG) to support this as a diagnosis. There were no additional findings to suggest one of the multi-system atrophies, and the age of onset is highly atypical for this group of diseases (which generally have their onset much later in life).
The coexistence of Parkinsonism and dystonia in a young Filipino male with a family history of "Parkinson's disease" (maternal grandfather) suggests the diagnosis of Lubag dystonia parkinsonism. This condition is characterized by progressive dystonia and parkinsonism beginning in midlife. It is an X-linked recessive disorder afflicting almost exclusively Filipino males. In the absence of features suggesting an alternative diagnosis, Lubag was felt to be the cause of this patient's symptoms.
Lubag is an X-linked recessive condition first described in 1976. It is found almost exclusively among Filipino males, most commonly those from the Visayan Islands. The island of Panay has the highest incidence of Lubag in the Philippines, where it is estimated to occur in 1 out of every 4,000 men. In the Ilonggo dialect, the disease is called "lubag" when there is intermittent twisting, "wa-eg" when there are sustained postures, and "sud-sud" when there is a shuffling gait. Although the gene has been localized to the Xq12-q21 region, the exact gene has not yet been determined.
Onset of symptoms usually occurs between 30-45 years of age, but has been reported in those as young as 14 years. Patients with the earliest onset of the disease tend to present with focal dystonia that usually generalizes within six years. Parkinsonism later develops in most cases. Late-onset cases can present with Parkinsonian features without dystonia. Routine laboratories, CT, and MRI are usually normal. PET may reveal nigrostriatal abnormalities. Mortality is usually due to associated dysphagia and aspiration pneumonia.
Autopsies have shown neuronal loss and multifocal mosaic astrocytosis of the caudate and lateral putamen. Interestingly, Lewy bodies are not prominent, as in idiopathic Parkinson's disease.
As might be expected from the locus of pathology (striatal involvement, rather than substantia nigra, resulting in loss of dopaminergic receptors), no medication, including dopaminergics, antidopaminergics, or antihistamines has had a consistent or lasting benefit. Some patients have reported improvements in bradykinesia and tremor when given dopaminergic agents; anticholinergics and benzodiazepenes have had only a slight effect on the generalized dystonia. Botulinum toxin is used for focal dystonia. The mainstay of treatment is physical therapy for improvement of gait and maintenance of range of motion.
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