Seizures in CBD: a case report (UCSF)

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CBD folks –
Here’s a case report out of UCSF of someone with a clinical diagnosis of CBD who had a seizure. The abstract says: “To our knowledge, however, there have been no reports of seizures associated with corticobasal degeneration (CBD).” Perhaps nothing has been published in the medical literature about this but there are plenty of case reports available on the CBD-related Yahoo!Group about seizures! I note that this patient had a brain biopsy where the results were “suggestive of CBD.” Of course the only conclusive diagnosis of CBD is available in a brain autopsy (upon death). On a living patient, a pathologist or surgeon can’t get to the right areas of the brain to confirm CBD. The risks of a brain biopsy are not insignificant; my impression is that a biopsy is done (on living patients) only in extreme cases.

Robin

Neurocase. 2009 Jun 18:1-5. [Epub ahead of print]

Seizures in corticobasal degeneration: A case report.

Douglas VC, Dearmond SJ, Aminoff MJ, Miller BL, Rabinovici GD.
Neurology Clinic, University of California, San Francisco, CA, USA.

Seizures are relatively common in Alzheimer disease (AD) and other neurodegenerative disorders. To our knowledge, however, there have been no reports of seizures associated with corticobasal degeneration (CBD). We describe a patient with brain biopsy features suggestive of CBD whose course was complicated by complex partial seizures with secondary generalization. Thus, the occurrence of seizures in a patient with dementia should not exclude the diagnosis of CBD.

PubMed ID#: 19544144 (see pubmed.gov for this free abstract only)

No LRRK2 mutations in 88 PSP patients (Germany)

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This recently-published abstract is on some German research into whether the LRRK2 genetic mutation occurs in PSP. This may be of most interest to those who participated in the 23andMe.com genetics testing.

I learned two things from the abstract:

* LRRK2 mutations “have been shown to be the most common genetic cause of both familial and sporadic Parkinson’s disease. Patients harboring LRRK2 mutations develop late onset PD that in most cases cannot be clinically distinguished from idiopathic PD.”

I thought LRRK2 was only associated with familial PD, and I thought familial PD was typically early-onset PD.

* “LRRK2 mutations have been reported to result in a broad spectrum of neuropathological alterations including progressive supranuclear palsy (PSP)-like Tau pathology.”

The weakness of this research is that the 88 PSP patients involved have a clinical diagnosis of PSP. The authors concluded that “there is no evidence that mutations in exon 31 of LRRK2 are a major risk factor for PSP. Our study, however, cannot rule out that other genetic variations in LRRK2 may be associated with PSP.”

Robin

European Journal of Neurology. 2009 Jun 15. [Epub ahead of print]

Screening for LRRK2 R1441 mutations in a cohort of PSP patients from Germany.

Madžar D, Schulte C, Gasser T.
Department of Neurodegenerative diseases, Hertie Institute for clinical brain research, University of Tuebingen, Tuebingen, Germany.

Background and purpose: Mutations in the leucine-rich repeat kinase gene (LRRK2) have been shown to be the most common genetic cause of both familial and sporadic Parkinson’s disease. Patients harboring LRRK2 mutations develop late onset PD that in most cases cannot be clinically distinguished from idiopathic PD.

Furthermore, LRRK2 mutations have been reported to result in a broad spectrum of neuropathological alterations including progressive supranuclear palsy (PSP)-like Tau pathology.

Methods: We screened a cohort of 88 clinically confirmed PSP patients for mutations in exon 31.

Results: We did not find any of the known mutations or any new variants.

Conclusions: Thus, there is no evidence that mutations in exon 31 of LRRK2 are a major risk factor for PSP. Our study, however, cannot rule out that other genetic variations in LRRK2 may be associated with PSP.

PubMed ID#: 19538213 (see pubmed.gov for this abstract only)

Pathology of corticobasal syndrome predictable in life?

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Here’s an interesting abstract of some research out of the UK. “Twelve patients with CBS [corticobasal syndrome] were followed prospectively; six had AD and six had classic CBD neuropathology.” Clinical records were reviewed for presenting symptoms. “Initial episodic memory complaints and poor performance on the combined orientation-memory subtest of the Addenbrooke’s Cognitive Examination (ACE) reliably predicted AD pathology while varying combinations of early frontal-lobe type behavioral symptoms, nonfluent language disturbance, orobuccal apraxia, and utilization behavior predicted CBD pathology ante-mortem.”
Robin

Movement Disorders. 2009 Jun 16. [Epub ahead of print]

Is the pathology of corticobasal syndrome predictable in life?

Shelley BP, Hodges JR, Kipps CM, Xuereb JH, Bak TH.
Department of Clinical Neurosciences, University of Cambridge, Addenbrooke’s Hospital, Cambridge, UK.

Corticobasal syndrome (CBS) has been associated with a heterogeneous spectrum of pathologies with an increasing number of reports of Alzheimer’s type pathology. There is, however, no means of predicting pathology of CBS in vivo at present. We compared the clinical features of patients presenting with CBS who have either pathologic changes of classic corticobasal degeneration (CBD) or Alzheimer’s disease (AD) at post-mortem to identify predictors of the specific pathological processes in life. Twelve patients with CBS were followed prospectively; six had AD and six had classic CBD neuropathology. After review of the presenting clinical features, we identified nine potential predictor variables, compared their frequency in the two groups, and performed a discriminant function analysis. Initial episodic memory complaints and poor performance on the combined orientation-memory subtest of the Addenbrooke’s Cognitive Examination (ACE) reliably predicted AD pathology while varying combinations of early frontal-lobe type behavioral symptoms, nonfluent language disturbance, orobuccal apraxia, and utilization behavior predicted CBD pathology ante-mortem. CBS is frequently associated with Alzheimer’s disease pathology. Early episodic memory impairment versus early behavioral symptomatology appears to best predict AD or CBD pathology in life. (c) 2009 Movement Disorder Society.

PubMed ID#: 19533751 (see pubmed.gov for this free abstract only)

orobuccal – “oro” refers to mouth and “buccal” refers to cheek

Severe memory impairment in CBD patient

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This article in a Korean-based journal notes that CBD patients typically have “relatively mild motor symptoms. … Our observations indicate that CBD can in rare cases present with severe episodic memory impairment associated with frontal executive dysfunctions in the early stage of illness.” This is a case report on one patient where the diagnosis of CBD has not been confirmed.
Robin

Journal of Clinical Neurology. 2008 Jun;4(2):94-8. Epub 2008 Jun 20.

Severe episodic memory impairment in a patient with clinical features compatible with corticobasal degeneration.

Kim SK, Park KW, Kang DY, Cha JK, Kim SH, Kim JW.
Department of Neurology, Dong-A University College of Medicine, Busan, Korea.

Corticobasal degeneration (CBD) is a progressive neurodegenerative disorder characterized by asymmetric parkinsonism associated with apraxia, cortical sensory loss, and alien-limb phenomenon. Neuropsychological testing in patients with CBD typically shows deficits in executive functions, praxis, language, and visuospatial functioning, but not in memory. We report a CBD patient with severely impaired memory function but relatively mild motor symptoms. Detailed neuropsychological assessment showed significant verbal and visual memory deficits accompanied by frontal executive dysfunctions. Our observations indicate that CBD can in rare cases present with severe episodic memory impairment associated with frontal executive dysfunctions in the early stage of illness.

PubMed ID#: 19513310 (see pubmed.gov for this abstract only; the abstract is available there for free)

Clinical heterogeneity in PSP (7 Japanese autopsy cases)

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These Japanese researchers investigated the clinical symptoms of seven autopsy-confirmed PSP cases. Amazingly, “only three patients (42.9%) matched the clinical diagnostic criteria of PSP” at the time of death. “In addition, only one patient (14.3%) matched these criteria at the time of the initial symptoms. Such underdiagnosis of PSP was mainly caused by heterogeneity, variety of the timing, and presence of symptoms in exclusion criteria. The present study also demonstrated that the clinical features of PSP may change dramatically according to the disease stage. Target symptoms should be selected based on time and stage to optimize patient quality of life.”
Robin

Neuropathology. 2009 Jun 7. [Epub ahead of print]

Clinical heterogeneity in progressive supranuclear palsy: Problems of clinical diagnostic criteria of NINDS-SPSP in a retrospective study of seven Japanese autopsy cases.

Sakamoto R, Tsuchiya K, Mimura M.
Department of Neuropsychiatry, Showa University School of Medicine, Setagaya-ku, Tokyo, Japan.

Progressive supranuclear palsy (PSP) is known to display variable atypical clinical features. In the absence of clinical markers to diagnose PSP, neuropathological examination is the “gold standard” for diagnosis.

We retrospectively investigated clinical features in seven autopsy-confirmed cases of PSP. Only three patients (42.9%) matched the clinical diagnostic criteria of PSP proposed by the National Institute of Neurological Disorders and Stroke and the Society for PSP (NINDS-SPSP) at the time of death. In addition, only one patient (14.3%) matched these criteria at the time of the initial symptoms. Such underdiagnosis of PSP was mainly caused by heterogeneity, variety of the timing, and presence of symptoms in exclusion criteria. The present study also demonstrated that the clinical features of PSP may change dramatically according to the disease stage. Target symptoms should be selected based on time and stage to optimize patient quality of life.

PubMed ID#: 19508347 (see pubmed.gov for this abstract only; the abstract is available for free there)