Presentation on theme: "Differential Diagnosis of Parkinsonism"— Presentation transcript:
1 Differential Diagnosis of Parkinsonism Katie Kompoliti, M.D.Associate ProfessorMovement Disorders SectionDepartment of Neurological SciencesRush University Medical Center
2 Parkinson’s Disease, Motor Abnormalities TremorBradykinesia/akinesiaCogwheel rigidityPostural instabilityParkinson disease is the most recognized of the movement disorders. Typically occurring in older indviduals, it is diagnosed clinically. The cardinal manifestations of Parkinson disease include the rest tremor, bradykinesia or slowness of movement and akinesia or lack of movement, muscle rigidity with a ratchety component, called cogwheeling and in advanced Parkinson disease, postural reflex impairment which causes difficulties with balance and falling. The gentleman shown in this slide has the typical posture of a patient with Parkinson disease. His posture is stooped, his elbows slightly flexed. He has a masked face and is walking slowly with a shuffle.
3 Parkinson’s Disease UKPDS Brain Bank Diagnostic Criteria Inclusion criteria parkinsonismBradykinesiaOne of the followingMuscular rigidityRest tremorPostural instabilitySupportive criteria for Parkinson’s DiseaseBegins on one sideRemains asymmetricRest tremor presentProgressive disorderResponds to levodopaNo atypical featuresBalance or falls in first yearEarly memory lossEarly hallucinationsEarly problems with blood pressure, potency or urinary symptoms
5 Pathology of Parkinson’s Disease On the left top is a picture of a normal midbrain with abundant pigmentation of the substantia nigra. Below that is the midbrain from a Parkinson’s disease patient with the substantia nigra depigmented. The second set at the top is the microscopic section of normal substantia nigra. Below that is the section from substantia nigra of a Parkinson’s patient. It shows profound loss of pigmented neurons and gliosis. On the extreme right is a pigmented neuron containing a Lewy body inclusion. The Lewy body is characterized by dense pink center and light pink periphery. Together, the loss of substantia nigra dopaminergic neurons and the presence of Lewy body inclusions are regarded as the hallmark of idiopathic Parkinson’s disease pathology.
6 DAT Scan to Differentiate Parkinson’s Disease from Essential Tremor
7 Early Parkinson’s disease Early featuresUnilateral rest tremorReduced spontaneous arm swingLoss of dexterity in one handLoss of facial expressionUnilateral foot dystonia (young onset)Pain in one shoulder
8 Advancing Parkinson disease Progression of PDIncreased severity of motor symptomsPostural reflex impairmentLoss of drug effectFreezing gaitDrug side effectsMotor fluctuationsDyskinesias
9 Parkinsonism, Differential Diagnosis Primary parkinsonismSecondary parkinsonismParkinsonism plus syndromesHeredofamiliar diseases
10 Parkinsonism, Differential Diagnosis Primary parkinsonismSecondary parkinsonismParkinsonism plus syndromesHeredofamiliar diseases
12 Juvenile Parkinsonism Onset before 21Heterogeneous disorderIn most cases distinct from IPDDystoniaSporadic or autosomal recessiveAutosomal recessivechromosome 6q, Parkin (Park 2)no Lewy bodies
13 Dopa-Responsive Dystonia Not a degenerative diseaseGTP-cyclohydrolase I geneClinical featuresabnormal gaitfocal limb dystoniascoliosisrest or postural tremorbradykinesiarigiditydiurnal fluctuationNormal PET or SPECT scansLevodopa responsiveGTP cyclohydrolase is the enzyme that is responsible for the synthesis of tetrahydrobiopterin, an important cofactor of TH
14 Parkinsonism, Differential Diagnosis Primary parkinsonismSecondary parkinsonismParkinsonism plus syndromesHeredofamiliar diseases
20 Subacute Sclerosing Panencephalitis-SSPE Progressive disorder 2-10 years after measlesCognitive, behavioral abnormalities, myoclonus, parkinsonism, coma, death (1-3 yrs)EEG periodic complexesHigh Ab titers in serum and CSFAtrophy, neuronal loss, lymphocytic infiltration, demyelination, gliosis, NFTsNuclear oligodendroglial inclusions, staining for viral Ag (NP and HA proteins)Post-infectious encephalomyelitis (2 wks post acute infection)Subacute neasles encephalitis (1-9 months after acute infection), immunosuppressed patientsNuclear inclusions formed in oligodendroglia (in acute encephalitis also seen in neurons and astrocytes)Ultrastructurally the nucleus is filled with rod- or spiral-shaped tube-like structures representing the nucleocapsid of measles virus
21 Periodic bursts of high-amplitude, slow-wave complexes with normal background rhythm Electroencephalogram (EEG) at the time of presentation in the neurology clinic (A) and 3 months later(B). The initial EEG (A) reveals periodic bursts of high-amplitude, slow-wave complexes. (Onset of the complexesis indicated by solid arrows; offset, by open arrows.) The background rhythm is normal, except for bifrontalslowing. This “burst-suppression” pattern is highly characteristic of subacute sclerosing panencephalitis
22 Transmissible Spongiform Encephalopathy Sporadic CJD, % of cases with MDCerebellar 70%Myoclonus 80%Extrapyramidal 56%Other (including tremor) 36%Brown P. Ann Neurol 1994Proposed conversion of normal to pathological isoform of prion protein. Strings denote unstructured regions, coils denote alpha-helical structure, ribbons denote beta-sheet structure. Note reduction of alpha helical structure and conversion to beta-sheet structureWith the exception of cerebellar, the others are rare early in the disease
24 Psychogenic Parkinsonism Not as frequentMaximal disability at onsetRigidity: voluntary resistance, no cogwheeling, distractibleBradykinesia: no fatiguing componentGait: atypical, arm held tightly to the trunk, exaggerated response to pull testTremor: same at rest, posture action, variability, distractibility, entrainmentCAUTION: Psychogenic parkinsonism has a high incidence of underlying Parkinson’s diseaseGTP cyclohydrolase is the enzyme that is responsible for the synthesis of tetrahydrobiopterin, an important cofactor of TH
25 Carbon Monoxide-Induced Parkinsonism Long-term exposure or severe acute exposureParkinsonism days to weeks laterTwo thirds complete recoveryOther neurological manifestationsmemory impairment, confabulationsemotional labilityapraxia, agnosiastupor, comahyperreflexiahomonymous hemianopiavestibular dysfunction
26 Carbon Monoxide-Induced Parkinsonism Carbon monoxide poisoning: Acute CO poisoning causes a cherry red discoloration of the brain and can also cause necrosis of the globus pallidus, as seen in this slide.
27 Mov Disord Sep;9(5):550-8.Neurological sequelae following carbon monoxide poisoning clinical course and outcome according to the clinical types and brain computed tomography scan findings.Lee MS, Marsden CD.Department of Neurology, Yongdong Severance Hospital, Yonsei University College of Medicine, Seoul, Korea.AbstractThe prognosis for patients who survive carbon monoxide (CO) poisoning is uncertain, particularly in those who develop persistent neurological complications after recovery from the initial coma. Thirty-one patients with the sequelae of CO poisoning, followed for a year, are described. Eight had a progressive course, and 23 had a delayed relapse after an initial recovery period of approximately 20 days (range, 1-36 days). Those with a progressive course developed a persistent akinetic-mute state, and four of the eight died. Those with the delayed relapsing course either developed a parkinsonian state with behavioral and cognitive impairment but could walk (nine cases), or progressed further to an akinetic-mute state, and were bed-bound (14 cases); the deterioration to either condition occurred rapidly over a few days to a week. Fourteen of the patients with the delayed relapses (61%) subsequently improved, but three (13%) died. Those with a progressive course without initial recovery were younger (mean age, 37.0 years) than those with a delayed relapsing course (55.2 years; p < 0.01). The mean duration of their initial coma (9.8 days) was longer than that in delayed relapsing cases (2.0 days; p < 0.01). The mean initial CO hemoglobin level was not different in the two groups. Brain computed tomography (CT) scans were obtained at the onset of sequelae in both groups. Ten patients had a normal CT scan, 13 had white matter low-density lesions, and four had globus pallidus low-density lesions.Yonsei Med J Jun 30;45(3):363-6.Chorea following acute carbon monoxide poisoning.Park S, Choi IS.Department of Neurology, Yonsei University College of Medicine, 134, Shinchon- dong, Seodaemoon-gu, Seoul , Korea.The clinical cases of 6 patients suffering with chorea after acute carbon monoxide (CO) poisoning were reviewed. There were 2 men and 4 women, and the age at onset ranged from 11 to 60 (mean 33.0) years. All the patients except one were associated with mild delayed CO encephalopathy. The latency period between CO poisoning and the onset of chorea was 10 to 30 (mean 21.7) days. The duration of chorea after CO poisoning was 14 to 90 (mean 39.8) days. The brain CT findings were bilateral low- density lesions in the basal ganglia and/or in the white matter of the cerebral cortex, and there was no correlation between the lesion sites on the imagings and the development of chorea. Neuroleptic agents alleviated the chorea and the patients did not relapse after neuroleptic agents were halted.
34 Dementia with Lewy Bodies Core features ParkinsonismDementiaWithin 1 year of onsetFluctuating cognitionpronounced variation in attention and alertnessRecurrent visual hallucinationsCortical Lewy BodiesUbiquitin ImmunocytochemistryLitvan, Mov Disord 2003;5:
35 Progressive Supranuclear Palsy Core Findings Progressive disorderAge onset > 40Often symmetric at onsetFalls in the first yearVertical supranuclear gaze palsyDysarthriaMinimal levodopa responseCognitive and behavioral problemsLitvan, Mov Disord 2003;5:
36 Progressive Supranuclear Palsy Gradually progressive parkinsonism, ≥ 40 yrs plus:Possible: vertical supranuclear palsy or slow vertical saccades+ falls < 1 yr of disease onsetProbable: vertical supranuclear palsy and falls < 1 yr of disease onsetDefinite: All criteria for possible or probable plus histopathological confirmationNINDS diagnostic criteria for PSP
41 Carriers of premutation alleles (55-200 CGG) Fragile X PremutationCarriers of premutation alleles ( CGG)Mild cognitive/behavioral deficitsPremature ovarian failureProgressive tremor, ataxia, parkinsonism, autonomic dysfunction ± peripheral neuropathy, memory, executive impairmentFragile X chromosomes are characterizied by satellite regions visible at the ends of metaphase chromosomes. These are due to a long series of CGG triplet repeats, as seen in Giemsa-stained (left) and scanning electron micrograph (right) material. Fragile X is associated with Martin-Bell Syndrome, the most common form of inherited mental retardationeosinophilic intranuclear inclusionsSymmetric T2 hyperintensities in MCP1/3 of male carriers over 50Protection due to random X inactivation of the premutation allele
43 X-linked Dystonia-Parkinsonism (Lubag) Men from the island of Panay4th-5th decade (as early as adolescence)Parkinsonism, action tremor, dystoniaPoor response to levodopaNeuronal loss in caudate, putamen, no LBsDYT3, Xq13.1
44 Juvenile Huntington’s Very high repeat length, paternal transmissionWestphal variantbradykinesiarigiditytremordystonic posturingataxiaseizuresmyoclonusmental regression
45 Summary Parkinsonism is a clinically defined syndrome. Parkinson’s disease is the most frequent cause of parkinsonismIn life, defined by clinical findingsNo diagnostic laboratory/imaging testsParkinsonism can occur as a part of many other disorders