CliniCian’s Corner
Case 2: Gait disturbance with unilateral intoeing
A
n eight-year-old healthy girl presented with progressive unilateral intoeing affecting her gait, for consideration of botulinum toxin injections for ‘monoplegic cerebral palsy’. At four years of age, her parents and teachers noticed that she was walking on the lateral border of her right foot. Developmental milestones were all met appropriately. She had already seen several specialists: two orthopedic surgeons, a neurologist, a neuromuscular specialist, two physiatrists and a developmental paediatrician. X-rays of the foot, two magnetic resonance imaging scans of her brain and spine, nerve conduction studies and genetic testing for Type 1 CharcotMarie-Tooth disease were normal. A diagnosis of cerebral palsy (CP) had been made. At eight years of age, the gait abnormality was worsening. She experienced frequent falls with leg bruising. The main findings on examination were posturing of the right foot in equinovarus position with a high arch. Posturing increased with voluntary opening and closing of the hand. There was increased tone in the right ankle plantar flexors and tibialis posterior, but it was not velocity dependent. There was early contracture through the right gastrocnemius and soleus. She was right handed and displayed no signs of right upper extremity hypertonia or clumsiness. A trial of medication was started based on a revised diagnosis. Within 24 h, her parents noted a subtle improvement in gait. Within one week, the patient’s gait had completely normalized.
Correspondence (Case 1): Dr Jackie Chiang, Department of Respiratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8. E-mail [email protected] Correspondence (Case 2): Dr Melissa Carter, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8. E-mail [email protected], [email protected] Case 1 accepted for publication June 14, 2012. Case 2 accepted for publication June 14, 2012
Paediatr Child Health Vol 17 No 10 December 2012
©2012 Pulsus Group Inc. All rights reserved
569
Clinician’s Corner
CASE 2 DiAgnoSiS: DopA-rESponSivE DyStoniA DuE to gtp CyClohyDrolASE 1 DEfiCiEnCy
The patient presented with the classic symptoms of dopa-responsive dystonia (DRD) caused by GTP cyclohydrolase 1 deficiency (1). The first sign is typically dystonia of one foot presenting as equinovarus posturing affecting gait, after a previously normal gait pattern. Diurnal fluctuation in the symptoms is a key finding in the early stages; patients often walk normally on waking in the morning, with progressive decline throughout the day. Apart from dystonia, on clinical examination, patients typically have brisk deep-tendon reflexes in the legs, and may exhibit ankle clonus and dystonic toe extension that can be mistaken for a positive Babinski sign. Thus, DRD is frequently misdiagnosed as spastic CP. CP is a group of disorders of the development of movement and posture, causing activity limitations that are attributed to nonprogressive disturbances that have occurred in the developing fetal or infant brain (2). Although etiologically heterogeneous, essential to the concept of CP is alterations in the child’s early development, typically before 18 months of age. Our patient’s presentation had some features consistent with CP, in that she had a motor disorder affecting her movement and posture resulting in activity limitations. However, there were features in her history that suggested the diagnosis of CP was incorrect. Most notably, the gait disturbance was noticed after four years of normal gross motor function; brain insults resulting in CP generally occur before the affected function (eg, walking) has developed. Furthermore, symptoms affecting only one leg would be unusual in CP; unilateral symptoms of hemiplegia typically affect both the upper and lower extremity. Finally, our patient’s presentation was one of a progressive motor disturbance, although this could not have been recognized until a few years had passed from her initial presentation. Another key finding in the present case was that of dystonia without spasticity. Dystonia and spasticity are two types of hypertonia, both of which are prevalent (and often coexist) in individuals with CP. A helpful tool for discriminating between spasticity and dystonia is the Hypertonia Assessment Tool (HAT) (3). The key features distinguishing spasticity and dystonia on physical examination of the affected limb are velocity-dependent resistance to stretch and the presence of spastic catch (for spasticity) and increased tone and involuntary postures of the limb with tactile stimulus or voluntary movement of a distant body part (for dystonia). The HAT takes less than 5 min to administer and is easily incorporated into the neurological examination performed in the clinic setting, as was the case for the present patient (the reader can download the HAT scoring chart and user manual from www. hollandbloorview.ca/research/Scientistprofiles/fehlings.php). Isolated unilateral foot dystonia in a child with otherwise normal gross motor development should trigger consideration of DRD as the underlying cause. The initiation of treatment with dopamine replacement is indicated and can also be diagnostic; small doses will generally lead to clinical improvement within days. Diagnosis can further be confirmed by genetic testing, as it was in our patient, and/or reduced levels of cerebral spinal fluid pterins. The cause of DRD in the present case was a deficiency of the enzyme GTP cyclohydrolase 1, which catalyzes the first step in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for tyrosine hydroxylase (TH) (1). TH converts L-tyrosine to
570
L-DOPA, which is then converted to dopamine in the central nervous system. Current recommendations for treatment of DRD begin with 1 mg/kg/day of L-DOPA (levodopa) plus a decarboxylase inhibitor (eg, carbidopa), which is increased slowly by small increments to avoid development of dyskinesias. Maximum benefit (complete or near-complete resolution of symptoms) is usually achieved with 4 mg/kg/day to 5 mg/kg/day in divided doses (4). Without treatment, DRD is a slowly but relentlessly progressive motor disorder, with dystonia spreading to other limb and trunk muscles. However, even advanced disease can respond dramatically to dopamine replacement. Dramatic response to L-DOPA can also be seen in other genetic disorders, namely autosomal recessive TH deficiency and autosomal dominant sepiapterin reductase-deficient DRD. These conditions are rare but are important to consider in the differential diagnosis because of treatment efficacy. Thus, in a patient with isolated dystonia presenting after normal development, a referral to a clinical geneticist or neurologist with expertise in movement disorders is recommended.
CliniCAl pEArlS • An atypical presentation of ‘dystonic CP’ requires consideration of rare conditions such as DRD, because there may be useful treatment options available aside from those typically recommended for CP. • It is important to distinguish the two common types of hypertonia in children (which may occur together in the same patient): spasticity and dystonia. The HAT is a clinically useful tool that can be used in the office and takes very little time to administer. • Consider a trial of L-DOPA in patients with dystonia, especially those with childhood-onset of symptoms, diurnal fluctuation, dystonia limited to one limb, and dystonia in a child with normal birth and developmental history and no suggestive etiology on brain imaging. This is one of the few chances physicians have to ‘cure’ CP. rEfErEnCES
1. Segawa M. Hereditary progressive dystonia with marked diurnal fluctuation. Brain Dev 2011;33:195-201. 2. Rosenbaum P, Paneth N, Leviton A, et al. A report: The definition and classification of cerebral palsy April 2006. Dev Med Child Neurol 2007;109:(Suppl);8-14. 3. Jethwa A, Mink J, MacArthur C, et al. Development of the Hypertonia Assessment Tool (HAT): A discriminative tool for hypertonia in children. Dev Med Child Neurol 2010;52:e83-7. 4. Mink JW. Dopa-responsive dystonia in children. Curr Treat Options Neuro 2003;5:279-82.
Melissa T Carter MD Division of Clinical and Metabolic Genetics, The Hospital for Sick Children Department of Paediatrics, University of Toronto, Darcy Fehlings MD Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital Department of Paediatrics, University of Toronto Toronto, Ontario
Paediatr Child Health Vol 17 No 10 December 2012
Case 2: Gait disturbance with unilateral intoeing
A
n eight-year-old healthy girl presented with progressive unilateral intoeing affecting her gait, for consideration of botulinum toxin injections for ‘monoplegic cerebral palsy’. At four years of age, her parents and teachers noticed that she was walking on the lateral border of her right foot. Developmental milestones were all met appropriately. She had already seen several specialists: two orthopedic surgeons, a neurologist, a neuromuscular specialist, two physiatrists and a developmental paediatrician. X-rays of the foot, two magnetic resonance imaging scans of her brain and spine, nerve conduction studies and genetic testing for Type 1 CharcotMarie-Tooth disease were normal. A diagnosis of cerebral palsy (CP) had been made. At eight years of age, the gait abnormality was worsening. She experienced frequent falls with leg bruising. The main findings on examination were posturing of the right foot in equinovarus position with a high arch. Posturing increased with voluntary opening and closing of the hand. There was increased tone in the right ankle plantar flexors and tibialis posterior, but it was not velocity dependent. There was early contracture through the right gastrocnemius and soleus. She was right handed and displayed no signs of right upper extremity hypertonia or clumsiness. A trial of medication was started based on a revised diagnosis. Within 24 h, her parents noted a subtle improvement in gait. Within one week, the patient’s gait had completely normalized.
Correspondence (Case 1): Dr Jackie Chiang, Department of Respiratory Medicine, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8. E-mail [email protected] Correspondence (Case 2): Dr Melissa Carter, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario M5G 1X8. E-mail [email protected], [email protected] Case 1 accepted for publication June 14, 2012. Case 2 accepted for publication June 14, 2012
Paediatr Child Health Vol 17 No 10 December 2012
©2012 Pulsus Group Inc. All rights reserved
569
Clinician’s Corner
CASE 2 DiAgnoSiS: DopA-rESponSivE DyStoniA DuE to gtp CyClohyDrolASE 1 DEfiCiEnCy
The patient presented with the classic symptoms of dopa-responsive dystonia (DRD) caused by GTP cyclohydrolase 1 deficiency (1). The first sign is typically dystonia of one foot presenting as equinovarus posturing affecting gait, after a previously normal gait pattern. Diurnal fluctuation in the symptoms is a key finding in the early stages; patients often walk normally on waking in the morning, with progressive decline throughout the day. Apart from dystonia, on clinical examination, patients typically have brisk deep-tendon reflexes in the legs, and may exhibit ankle clonus and dystonic toe extension that can be mistaken for a positive Babinski sign. Thus, DRD is frequently misdiagnosed as spastic CP. CP is a group of disorders of the development of movement and posture, causing activity limitations that are attributed to nonprogressive disturbances that have occurred in the developing fetal or infant brain (2). Although etiologically heterogeneous, essential to the concept of CP is alterations in the child’s early development, typically before 18 months of age. Our patient’s presentation had some features consistent with CP, in that she had a motor disorder affecting her movement and posture resulting in activity limitations. However, there were features in her history that suggested the diagnosis of CP was incorrect. Most notably, the gait disturbance was noticed after four years of normal gross motor function; brain insults resulting in CP generally occur before the affected function (eg, walking) has developed. Furthermore, symptoms affecting only one leg would be unusual in CP; unilateral symptoms of hemiplegia typically affect both the upper and lower extremity. Finally, our patient’s presentation was one of a progressive motor disturbance, although this could not have been recognized until a few years had passed from her initial presentation. Another key finding in the present case was that of dystonia without spasticity. Dystonia and spasticity are two types of hypertonia, both of which are prevalent (and often coexist) in individuals with CP. A helpful tool for discriminating between spasticity and dystonia is the Hypertonia Assessment Tool (HAT) (3). The key features distinguishing spasticity and dystonia on physical examination of the affected limb are velocity-dependent resistance to stretch and the presence of spastic catch (for spasticity) and increased tone and involuntary postures of the limb with tactile stimulus or voluntary movement of a distant body part (for dystonia). The HAT takes less than 5 min to administer and is easily incorporated into the neurological examination performed in the clinic setting, as was the case for the present patient (the reader can download the HAT scoring chart and user manual from www. hollandbloorview.ca/research/Scientistprofiles/fehlings.php). Isolated unilateral foot dystonia in a child with otherwise normal gross motor development should trigger consideration of DRD as the underlying cause. The initiation of treatment with dopamine replacement is indicated and can also be diagnostic; small doses will generally lead to clinical improvement within days. Diagnosis can further be confirmed by genetic testing, as it was in our patient, and/or reduced levels of cerebral spinal fluid pterins. The cause of DRD in the present case was a deficiency of the enzyme GTP cyclohydrolase 1, which catalyzes the first step in the biosynthesis of tetrahydrobiopterin (BH4), an essential cofactor for tyrosine hydroxylase (TH) (1). TH converts L-tyrosine to
570
L-DOPA, which is then converted to dopamine in the central nervous system. Current recommendations for treatment of DRD begin with 1 mg/kg/day of L-DOPA (levodopa) plus a decarboxylase inhibitor (eg, carbidopa), which is increased slowly by small increments to avoid development of dyskinesias. Maximum benefit (complete or near-complete resolution of symptoms) is usually achieved with 4 mg/kg/day to 5 mg/kg/day in divided doses (4). Without treatment, DRD is a slowly but relentlessly progressive motor disorder, with dystonia spreading to other limb and trunk muscles. However, even advanced disease can respond dramatically to dopamine replacement. Dramatic response to L-DOPA can also be seen in other genetic disorders, namely autosomal recessive TH deficiency and autosomal dominant sepiapterin reductase-deficient DRD. These conditions are rare but are important to consider in the differential diagnosis because of treatment efficacy. Thus, in a patient with isolated dystonia presenting after normal development, a referral to a clinical geneticist or neurologist with expertise in movement disorders is recommended.
CliniCAl pEArlS • An atypical presentation of ‘dystonic CP’ requires consideration of rare conditions such as DRD, because there may be useful treatment options available aside from those typically recommended for CP. • It is important to distinguish the two common types of hypertonia in children (which may occur together in the same patient): spasticity and dystonia. The HAT is a clinically useful tool that can be used in the office and takes very little time to administer. • Consider a trial of L-DOPA in patients with dystonia, especially those with childhood-onset of symptoms, diurnal fluctuation, dystonia limited to one limb, and dystonia in a child with normal birth and developmental history and no suggestive etiology on brain imaging. This is one of the few chances physicians have to ‘cure’ CP. rEfErEnCES
1. Segawa M. Hereditary progressive dystonia with marked diurnal fluctuation. Brain Dev 2011;33:195-201. 2. Rosenbaum P, Paneth N, Leviton A, et al. A report: The definition and classification of cerebral palsy April 2006. Dev Med Child Neurol 2007;109:(Suppl);8-14. 3. Jethwa A, Mink J, MacArthur C, et al. Development of the Hypertonia Assessment Tool (HAT): A discriminative tool for hypertonia in children. Dev Med Child Neurol 2010;52:e83-7. 4. Mink JW. Dopa-responsive dystonia in children. Curr Treat Options Neuro 2003;5:279-82.
Melissa T Carter MD Division of Clinical and Metabolic Genetics, The Hospital for Sick Children Department of Paediatrics, University of Toronto, Darcy Fehlings MD Division of Developmental Paediatrics, Holland Bloorview Kids Rehabilitation Hospital Department of Paediatrics, University of Toronto Toronto, Ontario
Paediatr Child Health Vol 17 No 10 December 2012
