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The youngest reported case of corticobasal degeneration
Parkinsonism and Related Disorders 10 (2003) 47–50 www.elsevier.com/locate/parkreldis
Case report
The youngest reported case of corticobasal degeneration Anna DePold Hohlera, Bruce R. Ransomb, Michael R. Chunc, Alexander I. Tro¨sterd, Ali Samiib,* b
a Department of Neurology, Madigan Army Medical Center, Tacoma, WA, USA Departments of Neurology, University of Washington, School of Medicine, VA Puget Sound Health Care System, 1660 South Columbian Way, Mailstop 127, Seattle, WA 98108, USA c The Everett Neurological Center, Everett, WA, USA d Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
Received 29 October 2002; revised 28 March 2003; accepted 9 April 2003
Abstract Corticobasal degeneration (CBD) is a movement disorder characterized by early apraxia and asymmetric parkinsonism that responds poorly to anti-Parkinson medications. There are clinical manifestations reflecting dysfunction in both the cerebral cortex and the basal ganglia. Patients typically present between the sixth and seventh decades. Previously, the youngest clinically diagnosed individual was 40 years old. Here we describe a 34-year-old woman who meets the clinical diagnostic criteria for CBD with onset of symptoms at age 28. In this patient, the first symptom was an ‘uncooperative’ right hand. This was soon followed by right hand dystonia. Symptoms progressed rapidly, and she developed generalized bradykinesia, rigidity, and corticospinal tract signs with preservation of the initial asymmetry. Her symptoms did not respond to a daily dose of 1200 mg of immediate release levodopa. Extensive laboratory workup and brain imaging were normal. Neuropsychological evaluation revealed mild deficits consistent with frontal-subcortical dysfunction. The chronic, progressive course, asymmetric limb rigidity, apraxia, focal dystonia, and lack of response to levodopa suggest CBD. To our knowledge, this is the youngest reported case of clinically probable CBD. q 2003 Elsevier Ltd. All rights reserved. Keywords: Corticobasal ganglionic degeneration; Corticobasal degeneration; Parkinson’s disease; Parkinson Plus syndrome; Young onset
1. Introduction Rebeiz first described corticobasal degeneration (CBD) in 1968 based on the pathologic findings of ‘corticodentatonigral degeneration with neuronal achromasia’ [1]. It is a movement disorder characterized by limb rigidity and dystonia, apraxia, gait difficulties, focal reflex myoclonus, eye movement abnormalities, pyramidal signs, dysarthria, alien limb phenomenon, and cortical sensory abnormalities. Patients typically have onset of symptoms in an arm, though a leg, gait or speech may more rarely be affected first. The patient often initially describes ‘clumsiness’ in the affected limb [2]. Dementia may occur later in the disease, though rarely it is the presenting symptom [3]. Neuropsychological evaluation may reveal asymmetric apraxia, executive dysfunction, and diminished retrieval of information from memory. Slowed informational processing and attentional * Corresponding author. Tel.: þ 1-206-764-2021; fax: þ1-206-764-2802. E-mail address: [email protected] (A. Samii). 1353-8020/03/$ - see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S1353-8020(03)00046-4
declines may also be noted [4,5]. The average age of onset is between 60 and 70 years. Here we report on the youngest case of clinically-probable CBD.
2. Case report The patient is a right hand dominant woman who in 1996, at the age of 28, developed right upper limb cramps, and difficulty performing fine motor tasks with the right hand. Her past medical and surgical histories were unremarkable. There was no history of smoking, alcohol abuse, or recreational drug use. There was no family history of neurologic disease. Initially, she was suspected of having carpal tunnel syndrome. Electrodiagnostic studies were normal. In 1997, she presented to one of the authors (MRC) complaining that her right hand ‘would not cooperate’. Her neurologic examination revealed breakdown of smooth pursuit eye movements, diminished right hand finger
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A. DePold Hohler et al. / Parkinsonism and Related Disorders 10 (2003) 47–50
movements, right foot dragging, and equivocal toe responses to plantar stimulation. She was diagnosed as having possible Parkinson’s disease. She was tried on carbidopa/levodopa, and the dose was titrated to 25/100 tid. She did not experience a significant motor benefit at this dose. At higher doses, her balance worsened without any motor improvement. Pramipexole was tried but she could not tolerate doses higher than 0.5 mg tid. Her motor symptoms did not improve on dopamine agonist therapy, and her condition continued to deteriorate. By 1999, a repeat examination by MRC revealed a masked face, severe right upper extremity rigidity, generalized bradykinesia, and postural instability. She was referred to the University of Washington Medical Center in the summer of 2000. On our evaluation, the patient was still taking pramipexole 0.5 mg tid without noticeable motor benefit. She weighed 110 lbs. Neurologic examination revealed broken down pursuit eye movements and hypometric saccades. She had mild limitation of ocular convergence and complained of difficulty focusing on objects in the range of 10– 25 cm from her face. She had markedly reduced facial animation, dysarthria, and hypophonia. Her right upper limb was dystonic and almost immobile, with sustained wrist, finger, and elbow flexion. Tendon contractures were present in finger flexors, wrist flexors, and the biceps tendon in the right upper limb. She had a right frozen shoulder with no mobility in that joint. Rigidity and bradykinesia were present in the left upper limb but to a much lesser degree compared to the right side. Sensory examination was entirely normal, including graphesthesia. Tendon reflexes were symmetric and not hyperactive, but she had bilateral Babinski signs. She required assistance as she stood up from a seated position. She used a wheeled walker and moved slowly and cautiously. Neuropsychological testing revealed average range of intelligence. Visual perception and language functions were generally well preserved. The patient performed below expectations on formal verbal fluency tasks (presumably secondary to slowed information processing and deficient spontaneous word retrieval strategy development, rather than aphasia). Memory was generally intact, although a weakness was observed in working memory. The patient had difficulties with a word list-learning task that places a premium on the development of sophisticated encoding strategies. Her interpretation of proverbs tended to be concrete, and she was occasionally slow in problem solving. At times she had difficulty keeping in mind solutions to a problem once she had derived the solution. Overall, the pattern of strengths and weaknesses was interpreted to be consistent with mild frontal-subcortical dysfunction. Moderately severe depression was also noted. Multiple attempts at dopaminergic pharmacotherapy as an outpatient failed to result in motor improvement in the face of adverse effects. The patient was therefore admitted to the University of Washington Medical Center for an inpatient trial of carbidopa/levodopa. The dose of
immediate-release carbidopa/levodopa 25/100 was titrated to three tablets four times daily over one week (1200 mg of immediate-release levodopa daily). Additional carbidopa (Lodosyn) 25 mg was required with each dose of carbidopa/levodopa to reduce nausea. The dose of levodopa could not be increased beyond 1200 mg daily because of nausea, vomiting, and fatigue. There was no improvement in any of the patient’s motor symptoms even at the highest tolerated dose of carbidopa/levodopa. The medication was discontinued rapidly with no deterioration of her motor symptoms. This suggested a lack of response to levodopa. Neuropsychological re-evaluation was limited during this admission by the patient’s motor state and speech dysfunction. A brief evaluation revealed a pattern of deficits consistent with that observed initially, with little interim progression of cognitive deficits. Over a five-year period, the patient’s motor symptoms progressed rapidly from normal motor function in 1996 to almost complete immobility by 2001. In September 2001, the patient was wheelchair bound and unable to stand or ambulate independently. She had markedly abnormal smooth pursuit and slow saccadic eye movements, but the range of her eye movements remained normal. She was dysarthric and severely hypophonic with slow tongue movements. Her limbs were nearly immobile bilaterally, and she guarded both of them because of pain. She had contractures at the shoulders, elbows, wrists, fingers, knees, and ankles bilaterally. Sensory examination remained completely normal. She had bilateral Babinski signs to plantar stimulation. The patient was completely dependent in all of her activities of daily living. Extensive laboratory work up including serum ceruloplasmin, serum copper, urinary copper excretion, and urine for heavy metals were all normal or negative. Genetic testing for the Parkin gene and Huntington disease were negative. Magnetic resonance imaging of the brain and the spinal cord were normal on multiple occasions over several years. The patient received no overall benefit from treatment with levodopa or a dopamine agonist. In an effort to decrease the pain resulting from her contractures, the patient was given a trial of botulinum toxin injections. She received limited benefit from one set of botulinum toxin injections given in December 2000 into the right upper extremity. The injections improved pain but not mobility. In July 2001, she underwent tendon release surgery involving the finger flexors of the right hand. Again, this helped reduce the pain but did not result in improved finger or hand mobility.
3. Discussion The differential diagnosis in this patient includes Parkinson’s disease (PD), CBD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA-P), young-onset
A. DePold Hohler et al. / Parkinsonism and Related Disorders 10 (2003) 47–50
(rigid-akinetic) Huntington disease, Wilson’s disease, and progressive subcortical gliosis [6,7]. PD is characterized by asymmetric rigidity, bradykinesia, tremor, and postural instability. Medication responsiveness is now one of the diagnostic criteria for PD [8]. This patient’s motor symptoms failed to respond to 1200 mg of immediaterelease levodopa (the highest dose she could tolerate), and there was no motor deterioration with levodopa discontinuation. PSP is a syndrome characterized by postural instability, extraocular movement abnormalities, and axial rigidity [9]. The symptoms are progressive, and patients do not respond significantly to levodopa. Vertical eye movements are more affected than horizontal eye movements. The presentation is typically symmetric. MSA-P has been divided into three subcategories based on the predominant clinical symptoms: autonomic (A), cerebellar (C), or striatonigral degeneration-predominant parkinsonism (P) [10,11]. The MSA-P subtype is included in this differential diagnosis. The parkinsonian features include bradykinesia with rigidity, postural instability, hypokinetic speech, and sometimes tremor. MSA patients also have a poor response to levodopa, but the presentation is typically symmetric. Rigid-akinetic Huntington disease (usually of youngonset) is characterized by symmetric rigidity and bradykinesia [12]. Diagnosis is based on family history, clinical presentation, and genetic testing. Family history and gene testing were negative in our patient. Wilson’s disease is described as hepatolenticular degeneration [13]. It affects the liver and causes movement disorders related to changes in the basal ganglia. Dystonia and cognitive changes can be seen with Wilson’s disease. No evidence of ocular or hepatic dysfunction was noted in this patient. Liver function testing, ceruloplasmin, serum and urine copper and magnetic resonance imaging were all normal. Progressive subcortical gliosis is a familial form of presenile frontotemporal dementia associated with mutations in the tau gene [14]. Parkinsonism may be a feature of the overall clinical picture. There is no family history of early dementia in our patient and her neuropsychological testing revealed only mild deficits in the setting of depression. The definitive diagnosis of CBD requires neuropathologic confirmation. The clinical diagnosis CBD remains a matter of debate. Riley and Lang divided the syndrome into clinically possible, probable, and definite CBD [15]. According to this gradation of diagnosis, the patient with ‘clinically-possible’ CBD must have three out of the four following criteria: chronic progressive course, asymmetric distribution, limb rigidity and limb apraxia. A ‘clinicallyprobable’ patient has all four of the above-mentioned signs plus two of the following: lack of response to levodopa, focal or asymmetric appendicular limb dystonia, myoclonus, and tremor. A ‘clinically-definite’ patient would also
49
show alien limb phenomenon, cortical sensory loss, or mirror movements. Alien limb is defined as a feeling that a limb is foreign and has a will of its own [16]. This is seen together with observable involuntary motor activity. Patients may find that their arm wanders uncontrollably, sometimes crossing the midline and interfering with the movement of the contralateral limb. While this patient did have a sense that her right limb ‘would not cooperate’, no definite involuntary motor activity was observed. The age of onset in CBD is 63 ^ 7.7 years of age [17]. The youngest clinically reported case is 40 years [2]. The youngest pathologically diagnosed case is 45 years [18]. We believe that the patient reported here meets the criteria for a diagnosis of clinically probable CBD [15]. The onset of symptoms at age 28, and diagnosis at age 32 makes this patient the youngest clinically described patient with CBD. References [1] Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968;18: 20–33. [2] Rinne JO, Lee MS, Thompson PD, Marsden CD. Corticobasal degeneration: a clinical study of 36 cases. Brain 1994;117: 1183– 96. [3] Grimes DA, Lang AE, Bergeron CB. Dementia as the most common presentation of corticobasal ganglionic degeneration. Neurology 1999;53:1969 –74. [4] Massman PJ, Kreiter KT, Jankovic J, Doody RS. Neuropsychological functioning in corticobasal ganglionic degeneration: differentiation from Alzheimer’s disease. Neurology 1996;46: 720 – 6. [5] Pillon B, Blin J, Vidailhet M, Deweer B, Sirigu A, Dubois B, Agid Y. The neuropsychlogical pattern of corticobasal ganglionic degeneration: comparison with progressive supranuclear palsy and Alzheimer’s disease. Neurology 1995;45:1477–83. [6] Stoessl AJ, Rivest J. Differential diagnosis of Parkinsonism. Can J Neurol Sci 1999;26(2):S1–S4. [7] Bhatia KP, Lee MS, Rinne JO, Revesz T, Scaravilli F, Davies L, Marsden CD. Corticobasal degeneration look-alikes. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in Neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 169–82. [8] Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson’s disease. Arch Neurol 1999;56:33– 9. [9] Rajput A, Rajput AH. Progressive supranuclear palsy: clinical features, pathophysiology and management. Drugs Aging 2001;18: 913–25. [10] Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163:94 – 8. [11] Hanna PA, Jankovic J, Kilpatrick JB. Multiple system atrophy, the putative causative role of environmental toxins. Arch Neurol 1999;56: 90–4. [12] Albin RL, Reiner A, Anderson KD, Penney JB, Young AB. Striatal and nigral neuron subpopulations in rigid Huntington’s disease: implications for the functional anatomy of chorea and rigidityakinesia. Ann Neurol 1990;27:357 –65.
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[13] Robertson WM. Wilson’s disease. Arch Neurol 2000;57:276– 7. [14] Goedert M, Spillantini MG, Crowther RA, Chen SG, Parchi P, Tabaton M, Lanska DJ, Markesbery WR, Wilhelmsen KC, Dickson DW, Petersen RB, Gambetti P. Tau gene mutation in familial progressive subcortical gliosis. Nat Med 1999;5:454 –7. [15] Riley DE, Lang AE. Clinical diagnostic criteria. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 29–34. [16] Hanna PA, Doody RS. Alien limb sign. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in
neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 135 –45. [17] Togasaki DM, Tanner CM. Epidemiologic aspects. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 53–9. [18] Wenning GK, Litvan I, Jankovic J, Granata R, Mangone CA, McKee A, Poewe W, Jellinger K, Ray Chaudhuri K, D’Olhaberriague L, Pearce RK. Natural history and survival of 14 patients with Corticobasal ganglionic degeneration confirmed at postmortem examination. J Neurol Neurosurg Psychiatry 1998;64:184– 9.
Case report
The youngest reported case of corticobasal degeneration Anna DePold Hohlera, Bruce R. Ransomb, Michael R. Chunc, Alexander I. Tro¨sterd, Ali Samiib,* b
a Department of Neurology, Madigan Army Medical Center, Tacoma, WA, USA Departments of Neurology, University of Washington, School of Medicine, VA Puget Sound Health Care System, 1660 South Columbian Way, Mailstop 127, Seattle, WA 98108, USA c The Everett Neurological Center, Everett, WA, USA d Psychiatry and Behavioral Sciences, University of Washington, Seattle, WA, USA
Received 29 October 2002; revised 28 March 2003; accepted 9 April 2003
Abstract Corticobasal degeneration (CBD) is a movement disorder characterized by early apraxia and asymmetric parkinsonism that responds poorly to anti-Parkinson medications. There are clinical manifestations reflecting dysfunction in both the cerebral cortex and the basal ganglia. Patients typically present between the sixth and seventh decades. Previously, the youngest clinically diagnosed individual was 40 years old. Here we describe a 34-year-old woman who meets the clinical diagnostic criteria for CBD with onset of symptoms at age 28. In this patient, the first symptom was an ‘uncooperative’ right hand. This was soon followed by right hand dystonia. Symptoms progressed rapidly, and she developed generalized bradykinesia, rigidity, and corticospinal tract signs with preservation of the initial asymmetry. Her symptoms did not respond to a daily dose of 1200 mg of immediate release levodopa. Extensive laboratory workup and brain imaging were normal. Neuropsychological evaluation revealed mild deficits consistent with frontal-subcortical dysfunction. The chronic, progressive course, asymmetric limb rigidity, apraxia, focal dystonia, and lack of response to levodopa suggest CBD. To our knowledge, this is the youngest reported case of clinically probable CBD. q 2003 Elsevier Ltd. All rights reserved. Keywords: Corticobasal ganglionic degeneration; Corticobasal degeneration; Parkinson’s disease; Parkinson Plus syndrome; Young onset
1. Introduction Rebeiz first described corticobasal degeneration (CBD) in 1968 based on the pathologic findings of ‘corticodentatonigral degeneration with neuronal achromasia’ [1]. It is a movement disorder characterized by limb rigidity and dystonia, apraxia, gait difficulties, focal reflex myoclonus, eye movement abnormalities, pyramidal signs, dysarthria, alien limb phenomenon, and cortical sensory abnormalities. Patients typically have onset of symptoms in an arm, though a leg, gait or speech may more rarely be affected first. The patient often initially describes ‘clumsiness’ in the affected limb [2]. Dementia may occur later in the disease, though rarely it is the presenting symptom [3]. Neuropsychological evaluation may reveal asymmetric apraxia, executive dysfunction, and diminished retrieval of information from memory. Slowed informational processing and attentional * Corresponding author. Tel.: þ 1-206-764-2021; fax: þ1-206-764-2802. E-mail address: [email protected] (A. Samii). 1353-8020/03/$ - see front matter q 2003 Elsevier Ltd. All rights reserved. doi:10.1016/S1353-8020(03)00046-4
declines may also be noted [4,5]. The average age of onset is between 60 and 70 years. Here we report on the youngest case of clinically-probable CBD.
2. Case report The patient is a right hand dominant woman who in 1996, at the age of 28, developed right upper limb cramps, and difficulty performing fine motor tasks with the right hand. Her past medical and surgical histories were unremarkable. There was no history of smoking, alcohol abuse, or recreational drug use. There was no family history of neurologic disease. Initially, she was suspected of having carpal tunnel syndrome. Electrodiagnostic studies were normal. In 1997, she presented to one of the authors (MRC) complaining that her right hand ‘would not cooperate’. Her neurologic examination revealed breakdown of smooth pursuit eye movements, diminished right hand finger
48
A. DePold Hohler et al. / Parkinsonism and Related Disorders 10 (2003) 47–50
movements, right foot dragging, and equivocal toe responses to plantar stimulation. She was diagnosed as having possible Parkinson’s disease. She was tried on carbidopa/levodopa, and the dose was titrated to 25/100 tid. She did not experience a significant motor benefit at this dose. At higher doses, her balance worsened without any motor improvement. Pramipexole was tried but she could not tolerate doses higher than 0.5 mg tid. Her motor symptoms did not improve on dopamine agonist therapy, and her condition continued to deteriorate. By 1999, a repeat examination by MRC revealed a masked face, severe right upper extremity rigidity, generalized bradykinesia, and postural instability. She was referred to the University of Washington Medical Center in the summer of 2000. On our evaluation, the patient was still taking pramipexole 0.5 mg tid without noticeable motor benefit. She weighed 110 lbs. Neurologic examination revealed broken down pursuit eye movements and hypometric saccades. She had mild limitation of ocular convergence and complained of difficulty focusing on objects in the range of 10– 25 cm from her face. She had markedly reduced facial animation, dysarthria, and hypophonia. Her right upper limb was dystonic and almost immobile, with sustained wrist, finger, and elbow flexion. Tendon contractures were present in finger flexors, wrist flexors, and the biceps tendon in the right upper limb. She had a right frozen shoulder with no mobility in that joint. Rigidity and bradykinesia were present in the left upper limb but to a much lesser degree compared to the right side. Sensory examination was entirely normal, including graphesthesia. Tendon reflexes were symmetric and not hyperactive, but she had bilateral Babinski signs. She required assistance as she stood up from a seated position. She used a wheeled walker and moved slowly and cautiously. Neuropsychological testing revealed average range of intelligence. Visual perception and language functions were generally well preserved. The patient performed below expectations on formal verbal fluency tasks (presumably secondary to slowed information processing and deficient spontaneous word retrieval strategy development, rather than aphasia). Memory was generally intact, although a weakness was observed in working memory. The patient had difficulties with a word list-learning task that places a premium on the development of sophisticated encoding strategies. Her interpretation of proverbs tended to be concrete, and she was occasionally slow in problem solving. At times she had difficulty keeping in mind solutions to a problem once she had derived the solution. Overall, the pattern of strengths and weaknesses was interpreted to be consistent with mild frontal-subcortical dysfunction. Moderately severe depression was also noted. Multiple attempts at dopaminergic pharmacotherapy as an outpatient failed to result in motor improvement in the face of adverse effects. The patient was therefore admitted to the University of Washington Medical Center for an inpatient trial of carbidopa/levodopa. The dose of
immediate-release carbidopa/levodopa 25/100 was titrated to three tablets four times daily over one week (1200 mg of immediate-release levodopa daily). Additional carbidopa (Lodosyn) 25 mg was required with each dose of carbidopa/levodopa to reduce nausea. The dose of levodopa could not be increased beyond 1200 mg daily because of nausea, vomiting, and fatigue. There was no improvement in any of the patient’s motor symptoms even at the highest tolerated dose of carbidopa/levodopa. The medication was discontinued rapidly with no deterioration of her motor symptoms. This suggested a lack of response to levodopa. Neuropsychological re-evaluation was limited during this admission by the patient’s motor state and speech dysfunction. A brief evaluation revealed a pattern of deficits consistent with that observed initially, with little interim progression of cognitive deficits. Over a five-year period, the patient’s motor symptoms progressed rapidly from normal motor function in 1996 to almost complete immobility by 2001. In September 2001, the patient was wheelchair bound and unable to stand or ambulate independently. She had markedly abnormal smooth pursuit and slow saccadic eye movements, but the range of her eye movements remained normal. She was dysarthric and severely hypophonic with slow tongue movements. Her limbs were nearly immobile bilaterally, and she guarded both of them because of pain. She had contractures at the shoulders, elbows, wrists, fingers, knees, and ankles bilaterally. Sensory examination remained completely normal. She had bilateral Babinski signs to plantar stimulation. The patient was completely dependent in all of her activities of daily living. Extensive laboratory work up including serum ceruloplasmin, serum copper, urinary copper excretion, and urine for heavy metals were all normal or negative. Genetic testing for the Parkin gene and Huntington disease were negative. Magnetic resonance imaging of the brain and the spinal cord were normal on multiple occasions over several years. The patient received no overall benefit from treatment with levodopa or a dopamine agonist. In an effort to decrease the pain resulting from her contractures, the patient was given a trial of botulinum toxin injections. She received limited benefit from one set of botulinum toxin injections given in December 2000 into the right upper extremity. The injections improved pain but not mobility. In July 2001, she underwent tendon release surgery involving the finger flexors of the right hand. Again, this helped reduce the pain but did not result in improved finger or hand mobility.
3. Discussion The differential diagnosis in this patient includes Parkinson’s disease (PD), CBD, progressive supranuclear palsy (PSP), multiple system atrophy (MSA-P), young-onset
A. DePold Hohler et al. / Parkinsonism and Related Disorders 10 (2003) 47–50
(rigid-akinetic) Huntington disease, Wilson’s disease, and progressive subcortical gliosis [6,7]. PD is characterized by asymmetric rigidity, bradykinesia, tremor, and postural instability. Medication responsiveness is now one of the diagnostic criteria for PD [8]. This patient’s motor symptoms failed to respond to 1200 mg of immediaterelease levodopa (the highest dose she could tolerate), and there was no motor deterioration with levodopa discontinuation. PSP is a syndrome characterized by postural instability, extraocular movement abnormalities, and axial rigidity [9]. The symptoms are progressive, and patients do not respond significantly to levodopa. Vertical eye movements are more affected than horizontal eye movements. The presentation is typically symmetric. MSA-P has been divided into three subcategories based on the predominant clinical symptoms: autonomic (A), cerebellar (C), or striatonigral degeneration-predominant parkinsonism (P) [10,11]. The MSA-P subtype is included in this differential diagnosis. The parkinsonian features include bradykinesia with rigidity, postural instability, hypokinetic speech, and sometimes tremor. MSA patients also have a poor response to levodopa, but the presentation is typically symmetric. Rigid-akinetic Huntington disease (usually of youngonset) is characterized by symmetric rigidity and bradykinesia [12]. Diagnosis is based on family history, clinical presentation, and genetic testing. Family history and gene testing were negative in our patient. Wilson’s disease is described as hepatolenticular degeneration [13]. It affects the liver and causes movement disorders related to changes in the basal ganglia. Dystonia and cognitive changes can be seen with Wilson’s disease. No evidence of ocular or hepatic dysfunction was noted in this patient. Liver function testing, ceruloplasmin, serum and urine copper and magnetic resonance imaging were all normal. Progressive subcortical gliosis is a familial form of presenile frontotemporal dementia associated with mutations in the tau gene [14]. Parkinsonism may be a feature of the overall clinical picture. There is no family history of early dementia in our patient and her neuropsychological testing revealed only mild deficits in the setting of depression. The definitive diagnosis of CBD requires neuropathologic confirmation. The clinical diagnosis CBD remains a matter of debate. Riley and Lang divided the syndrome into clinically possible, probable, and definite CBD [15]. According to this gradation of diagnosis, the patient with ‘clinically-possible’ CBD must have three out of the four following criteria: chronic progressive course, asymmetric distribution, limb rigidity and limb apraxia. A ‘clinicallyprobable’ patient has all four of the above-mentioned signs plus two of the following: lack of response to levodopa, focal or asymmetric appendicular limb dystonia, myoclonus, and tremor. A ‘clinically-definite’ patient would also
49
show alien limb phenomenon, cortical sensory loss, or mirror movements. Alien limb is defined as a feeling that a limb is foreign and has a will of its own [16]. This is seen together with observable involuntary motor activity. Patients may find that their arm wanders uncontrollably, sometimes crossing the midline and interfering with the movement of the contralateral limb. While this patient did have a sense that her right limb ‘would not cooperate’, no definite involuntary motor activity was observed. The age of onset in CBD is 63 ^ 7.7 years of age [17]. The youngest clinically reported case is 40 years [2]. The youngest pathologically diagnosed case is 45 years [18]. We believe that the patient reported here meets the criteria for a diagnosis of clinically probable CBD [15]. The onset of symptoms at age 28, and diagnosis at age 32 makes this patient the youngest clinically described patient with CBD. References [1] Rebeiz JJ, Kolodny EH, Richardson EP. Corticodentatonigral degeneration with neuronal achromasia. Arch Neurol 1968;18: 20–33. [2] Rinne JO, Lee MS, Thompson PD, Marsden CD. Corticobasal degeneration: a clinical study of 36 cases. Brain 1994;117: 1183– 96. [3] Grimes DA, Lang AE, Bergeron CB. Dementia as the most common presentation of corticobasal ganglionic degeneration. Neurology 1999;53:1969 –74. [4] Massman PJ, Kreiter KT, Jankovic J, Doody RS. Neuropsychological functioning in corticobasal ganglionic degeneration: differentiation from Alzheimer’s disease. Neurology 1996;46: 720 – 6. [5] Pillon B, Blin J, Vidailhet M, Deweer B, Sirigu A, Dubois B, Agid Y. The neuropsychlogical pattern of corticobasal ganglionic degeneration: comparison with progressive supranuclear palsy and Alzheimer’s disease. Neurology 1995;45:1477–83. [6] Stoessl AJ, Rivest J. Differential diagnosis of Parkinsonism. Can J Neurol Sci 1999;26(2):S1–S4. [7] Bhatia KP, Lee MS, Rinne JO, Revesz T, Scaravilli F, Davies L, Marsden CD. Corticobasal degeneration look-alikes. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in Neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 169–82. [8] Gelb DJ, Oliver E, Gilman S. Diagnostic criteria for Parkinson’s disease. Arch Neurol 1999;56:33– 9. [9] Rajput A, Rajput AH. Progressive supranuclear palsy: clinical features, pathophysiology and management. Drugs Aging 2001;18: 913–25. [10] Gilman S, Low PA, Quinn N, Albanese A, Ben-Shlomo Y, Fowler CJ, Kaufmann H, Klockgether T, Lang AE, Lantos PL, Litvan I, Mathias CJ, Oliver E, Robertson D, Schatz I, Wenning GK. Consensus statement on the diagnosis of multiple system atrophy. J Neurol Sci 1999;163:94 – 8. [11] Hanna PA, Jankovic J, Kilpatrick JB. Multiple system atrophy, the putative causative role of environmental toxins. Arch Neurol 1999;56: 90–4. [12] Albin RL, Reiner A, Anderson KD, Penney JB, Young AB. Striatal and nigral neuron subpopulations in rigid Huntington’s disease: implications for the functional anatomy of chorea and rigidityakinesia. Ann Neurol 1990;27:357 –65.
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A. DePold Hohler et al. / Parkinsonism and Related Disorders 10 (2003) 47–50
[13] Robertson WM. Wilson’s disease. Arch Neurol 2000;57:276– 7. [14] Goedert M, Spillantini MG, Crowther RA, Chen SG, Parchi P, Tabaton M, Lanska DJ, Markesbery WR, Wilhelmsen KC, Dickson DW, Petersen RB, Gambetti P. Tau gene mutation in familial progressive subcortical gliosis. Nat Med 1999;5:454 –7. [15] Riley DE, Lang AE. Clinical diagnostic criteria. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 29–34. [16] Hanna PA, Doody RS. Alien limb sign. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in
neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 135 –45. [17] Togasaki DM, Tanner CM. Epidemiologic aspects. In: Litvan I, Goetz CG, Lang AE, editors. Corticobasal degeneration. Advances in neurology, vol. 82. Philadelphia: Lippincott Williams and Wilkins; 2000. p. 53–9. [18] Wenning GK, Litvan I, Jankovic J, Granata R, Mangone CA, McKee A, Poewe W, Jellinger K, Ray Chaudhuri K, D’Olhaberriague L, Pearce RK. Natural history and survival of 14 patients with Corticobasal ganglionic degeneration confirmed at postmortem examination. J Neurol Neurosurg Psychiatry 1998;64:184– 9.