Diagrama de flujo para evaluacin de Corea

Ruth H. Walker, MB., Ch.B., Ph.D.

Departments of Neurology, James J. Peters Veterans Affairs Medical Center, Bronx, NY, and Mount Sinai School of Medicine, New York, NY
ruth.walker@mssm.edu
Pacientes con
Estreptoccica?
corea Edad Beb/nio Dolor de
garganta,cardiopata
+ve
Autosmico recesivo /espordico de Sydenham's chorea
reumtica ASO/ALSO,
Sndrome deLesch-Nyhan inicio? anti-DNAasa B titulada.
confirmacin con prueba
gentica Tardive dyskinesia
Adulto
Ligado al Hereditario ? Autosmico Normal
cromosoma X Recesivo
Delayed

Inicio en la Autosmica Medication- Yes Direct

Prueba S infancia, artritis dominante Time course?
MRI; normal induced? Immediate or side effect
cido rico gotosa,
automutilacin Fe in basal dose related
Calcium Acute infarct in
? ganglia ? deposition posterior limb of
in basal internal capsule.
ganglia. Diffusion- No
No Pantothenate Phospholipase-associated CT scan weighted MRI
Normal neurodegeneration
kinase-associated Yes No Infantile bilateral
neurodegeneration Yes Structural lesion;
striatal necrosis
Mix blood 1:1 with 0.9% NaCl containing 10IU/ml heparin
Incubate at room temperature for 30-120 min on a shaker Childhood onset
Take 5+ microphotographs from each wet preparation Yes
PKAN: T2 weighted MRI
Stroke, tumor
(phase-contrast microscope)
Occasional later onset
Pigmentary retinopathy
MRI arteriovenous malformation, Leighs syndrome,
Lactate/
Count cells with spicules: normal value < 6.3 % Dystonia
PANK2 Normal PLA2G6 calcification (IBG1?), other mitochrondial?
No S Lubag 10% have acanthocytosis
mutation? No Ceruloplasmin?
mutation?
pyruvate
No etc Confirm with gene test
Acantocitosis? Filipino? Confirmacin
con prueba
gentica Basal ganglia
No No
Typical phenotype = dystonia- necrosis?
parkinsonism, but should be Other
S considered in any Filipino with an
neurodegeneration with
unexplained movement disorder, Caudate Yes
including women Yes brain iron Accumulation nucleus
Recent Post-infectious
disorder FAHN, MPAN, Yes infection? striatal necrosis
Full panel of 23 Kell abs usually available atrophy?
at regional blood centers;
BPAN
Aceruloplasminemia
Courtesy of Dr Hans H. Jung, Zrich
Ask to exclude McLeod phenotype
Pseudo-
dominant Features
Yes
Enzimas inheritance?
Iron overload suggestive of Yes Work-up for inherited
Diabetes mellitus in 20s (from pancreatic iron)
hepticas o Kx and Kell Middle-age onset metabolic
Sndrome McLeod disease? metabolic diseases;
creatina ags
Retinal degeneration (from iron deposition)
Behavioural changes/
Parkinsonism/dystonia, orofacial involvement is typical organic/amino acids,
quinasa Dementia usually later
psychopathology
Seizures Fasano et al. 2008 MRI may not show Fe accumulation (Skidmore et al. 2007) lysosomal enzymes
Peripheral neuropathy Gradient echo T2*
skin biopsy etc
Normal Hyporeflexia No
Normal Cardiomyopathy No Normal
Hepatosplenomegaly
?
Normal Kayser- Normal
McNeill et al 2008
Fast spin echo Fleischer Ceruloplasmin? Creatine kinase Liver enzymes
rings? Diagnosis Diagnosis
Yes Ferritin 24hr Cu
Lactato/ Normal mutations?
Ensayo de chorein excretion?
piruvato Normal Chorein Normal
Dobson-Stone et al. 2004
Normal
Contact danek@lmu.de
Recent
Neuroferritinopathy No +ve +ve
+ve liver
disease?
No Metabolic
Middle-age onset
Wilsons disease
Parkinsonism/dystonia
Occasional ataxia, spasticity
Ataxia? work-up (2) Metabolic
Dystonia/parkinsonism/dystonia more common Normal work-up (1)
Anti-phospholipid ab Normal
Dementia rare
Adolescent onset Electrolytes
Risus sardonicus
Mitochondrial Chorea-acanthocytosis Psychiatric disease Yes
SLE, other autoimmune Glucose
Yes Polycythemia vera Pregnancy test
disorder? Confirmacin con prueba
huntingtin Celiac disease TSH
Confirm with gene gentica mutation? Normal Acquired hepatocerebral HIV, B12, RPR
Pb
test Behavioural changes/psychiatric disease But can be normal
in pre-menopausal
degeneration Frataxin
Self-mutilation of lips, tongue, other body parts
Seizures women with
mutation?
Friedreichs ataxia
Hyporeflexia Ferritin level? neuroferritinopathy
Hepatomegaly No Onset in childhood
Huntingtons Ataxia may be absent
Chorea is a common movement disorder, the etiology of which is Reflexes increased or decreased
disease Cardiomyopathy Onset in childhood
rarely identifiable from its appearance. The identification of genetic Susceptible to radiation
Risk of malignancy, infection

Courtesy Dr Jane Zheng, UNC-CH

causes for some of the inherited choreas has facilitated their Elevated -feto-protein

C9ORF2 C9ORF72 diagnosis, in addition to increasing the spectrum of phenotypes for Ataxia-telangiectasia
Telangiectasia?
mutation? disease other disorders in which chorea may occur less often. A number of Confirm with ATM mutation
Variable phenotype clues in the family and medical history, clinical examination, and
Often upper motor neuron
signs laboratory findings may inform the diagnosis. Whilst we typically
No Reduced penetrance
Variable age of onset consider these simultaneously when evaluating the patient with
chorea, there is a need for an algorithm to generate consideration -feto- Senataxin Yes Ataxia with oculomotor
of some of the rarer etiologies. protein mutation? apraxia type 2
African
Onset in childhood
Huntingtons Yes Junctophilin-3 Yes ancestry? No Peripheral neuropathy

disease-like 2 mutation? (may be This flow chart aims to present the various factors which facilitate Elevated creatine kinase

occult) making the correct diagnosis, and the appropriate testing to Consider AD
Consider AD
Behavioural changes/psychiatric disease Aprataxin spinocerebellar
May have more dystonia/parkinsonism? consider depending upon previous test results. The list of mutation?
ataxias
and X-linked
pathways
10% have acanthocytosis e.g.
No differential diagnoses of chorea is ever-evolving with advances in homozygosity?
the molecular biology of movement disorders. This algorithm Yes
Spinocerebellar ataxia MRI - Fe which is open to further development in the light of new Autoimmune
Yes SCA/DRPLA No Yes Ataxia with oculomotor
1,2,3,17,? in basal knowledge. non-paraneoplastic
mutations? apraxia type 1
DRPLA Onset in childhood syndrome
ganglia This flow chart does not necessarily indicate the temporal course Peripheral neuropathy Neoplasm Negative workup
Ataxia, eye movement abormalities,
Elevated cholesterol
peripheral neuropathy etc are typical, but may
of the diagnostic work-up of chorea, especially if the family history evaluation;
be pure HD phenocopy No hypoalbuminemia
Anti-Hu, Yo, +ve Paraneoplastic
Yes Huntingtons
DRPLA myoclonus, dementia, dystonia
typical is not known, but should be used a guideline to generate the CRMP-5, GAD65 syndrome
disease-like 1?
consideration of various clinical entities in light of the available NMDA, VGCC
Caspr2, LGI-1
Benign hereditary information. .. Creutzfeldt-Jakob
chorea Yes Non- No Prion Single Yes PLEDs? disease
Confirm with TITF-1 MRI findings?
+ve
progressive, mutation? (chorea more common
mutation, although other -ve CSF 14-3-3
no dementia? case? in new variant)
genes implicated Consider atypical forms of
No No AD, X-linked or AR disorders, Confirmed by
depending upon inheritance -ve pathology
?