Hereditary spastic paraplegia - Clinicals, Diagnosis, and Management

Neurology

Clinicals - History

Fact Explanation
Introduction to the disease The hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous disorder that characterized by lower extremity spasticity and weakness. There are several classifications of HSP. It can be classify clinically as uncomplicated or complicated and genetically by mode of inheritance,causative mutation as well as chromosomal locus.. Introduction to the disease
The hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous disorder that characterized by lower extremity spasticity and weakness. There are several classifications of HSP. It can be classify clinically as uncomplicated or complicated and genetically by mode of inheritance,causative mutation as well as chromosomal locus..
Family history of HSP Since it is genetically heterogeneous family history may play an important role. It can be inherited in autosomal dominant, autosomal recessive, X-linked as well as mitochondrial inheritance manner.. Family history of HSP
Since it is genetically heterogeneous family history may play an important role. It can be inherited in autosomal dominant, autosomal recessive, X-linked as well as mitochondrial inheritance manner..
Lower extremity weakness and spasticity This is the most predominant feature of HSP which occurs in variable proportions. So that it resembles spastic diplegic cerebral palsy if symptoms start at very early childhood. If symptoms begin later it may progress slowly and steadily.Progressive lower extremity spastic weakness is a characteristic feature of pure HSP.. Lower extremity weakness and spasticity
This is the most predominant feature of HSP which occurs in variable proportions. So that it resembles spastic diplegic cerebral palsy if symptoms start at very early childhood. If symptoms begin later it may progress slowly and steadily.Progressive lower extremity spastic weakness is a characteristic feature of pure HSP..
Difficulty in walking Affected individuals commonly develop difficulty in walking. It may either be non progressive or worsen insidiously.So that the patient often need wheelchairs, canes and walkers.. Difficulty in walking
Affected individuals commonly develop difficulty in walking. It may either be non progressive or worsen insidiously.So that the patient often need wheelchairs, canes and walkers..
Urinary sphincter disturbance Seen among 50% of patients. This commonly manifest as a combination of as urgency, frequency and hesitancy. Commonly seen among patients with long standing disease.. Urgency is commonly seen in classic HSP. Occurs due to hypertonic urinary bladder. This can be either non progressive or slowly progressive. Urinary sphincter disturbance
Seen among 50% of patients. This commonly manifest as a combination of as urgency, frequency and hesitancy. Commonly seen among patients with long standing disease.. Urgency is commonly seen in classic HSP. Occurs due to hypertonic urinary bladder. This can be either non progressive or slowly progressive.
Paresthesia Paresthesia in lower extremity can recognized in pure HSP.. Paresthesia
Paresthesia in lower extremity can recognized in pure HSP..
Sensory neuropathy and Ulcers Found in complicated HSP. Sensory neuropathy either can be asymptomatic which detect only by clinical examination, childhood onset or adult onset. Chronic painless cutaneous ulcers and neuropathic bone resorption found to be occur in some patients in their early childhood. Long standing established spastic paraparesis may cause less severe form of tropic skin changes and ulcers on the feet in their adult life.. Sensory neuropathy and Ulcers
Found in complicated HSP. Sensory neuropathy either can be asymptomatic which detect only by clinical examination, childhood onset or adult onset. Chronic painless cutaneous ulcers and neuropathic bone resorption found to be occur in some patients in their early childhood. Long standing established spastic paraparesis may cause less severe form of tropic skin changes and ulcers on the feet in their adult life..
Seizures / Epilepsy Found to be occur in complicated HSP.. Studies has bee found epilepsy syndromes and HSP seem to be closely associated. Exact pathology is not clear and there is no exact association with specific seizure type but myoclonic, simple partial, complex partial, as well as generalised epilepsy have been reported. HSP also found to inherited in mitochondrial inheritance manner and epilepsy is a characteristic feature of those mitochondrial diseases.. Seizures / Epilepsy
Found to be occur in complicated HSP.. Studies has bee found epilepsy syndromes and HSP seem to be closely associated. Exact pathology is not clear and there is no exact association with specific seizure type but myoclonic, simple partial, complex partial, as well as generalised epilepsy have been reported. HSP also found to inherited in mitochondrial inheritance manner and epilepsy is a characteristic feature of those mitochondrial diseases..
Intellectual disability Recognized feature of complicated HSP.. Intellectual disability
Recognized feature of complicated HSP..
Dementia Seen among patients with complicated HSP.. It has also been reported in both autosomal dominant as well as recessive families. Some studies suggest that sub cortical dementia may characterize the complicated HSP phenotype of spastic paraplegia with dementia.. Dementia
Seen among patients with complicated HSP.. It has also been reported in both autosomal dominant as well as recessive families. Some studies suggest that sub cortical dementia may characterize the complicated HSP phenotype of spastic paraplegia with dementia..
Microcephaly The presence of microcephaly suggestive of early onset illness affecting brain growth and development. But it is found to be uncommon in adult onset HSP because they initially had normal brain growth and development so that the normal head size.. Microcephaly
The presence of microcephaly suggestive of early onset illness affecting brain growth and development. But it is found to be uncommon in adult onset HSP because they initially had normal brain growth and development so that the normal head size..
Amyotrophy Seen in patients with complicated HSP. Wasting of small muscles of the hand can be recognized. Sometimes it may resembles hereditary motor and sensory neuropathy. ,. Amyotrophy
Seen in patients with complicated HSP. Wasting of small muscles of the hand can be recognized. Sometimes it may resembles hereditary motor and sensory neuropathy. ,.
Dysmetria Occurs due to cerebellar involvement. A trace of terminal dysmetria may sometimes found in the upper limbs However affected individuals do not show more florid cerebellar signs.. Dysmetria
Occurs due to cerebellar involvement. A trace of terminal dysmetria may sometimes found in the upper limbs However affected individuals do not show more florid cerebellar signs..
Ataxia Can be seen in complicated HSP due to underline cerebellar involvement.,. Ataxia
Can be seen in complicated HSP due to underline cerebellar involvement.,.
Dysarthria Recognized feature of complicated HSP. Occurs due to cerebellar involvement. Speech impairments and delayed language development found to be occurred.,. Dysarthria
Recognized feature of complicated HSP. Occurs due to cerebellar involvement. Speech impairments and delayed language development found to be occurred.,.
Icthyosis Seen in complicated HSP. Associated with mental retardation and occasionally with pigmentary macular degeneration.. Icthyosis
Seen in complicated HSP. Associated with mental retardation and occasionally with pigmentary macular degeneration..
Pes cavus It is an uncommon finding. Finding itself reflect the duration as well as severity of the disease.. Pes cavus
It is an uncommon finding. Finding itself reflect the duration as well as severity of the disease..

Clinicals - Examination

Fact Explanation
Spastic weakness Occurs due to corticospinal tract deficit that affecting both lower extremities. Spasticity is maximally seen in muscles such as hamstrings, quadriceps, adductors, gastrocnemius and soleus Where the weakness is commonly demonstrated in iliopsoas, hamstring, and tibialis anterior muscles. It can be variable. Some may have spasticity without demonstrable weakness, whereas the others may have spasticity and weakness in similar proportions.. Spastic weakness
Occurs due to corticospinal tract deficit that affecting both lower extremities. Spasticity is maximally seen in muscles such as hamstrings, quadriceps, adductors, gastrocnemius and soleus Where the weakness is commonly demonstrated in iliopsoas, hamstring, and tibialis anterior muscles. It can be variable. Some may have spasticity without demonstrable weakness, whereas the others may have spasticity and weakness in similar proportions..
Hyperreflexia, Commonly seen in lower limbs due to deficit in corticospinal tract. Axon degeneration maximaly at the distal ends of the corticospinal tracts is the underline pathology.. In early part of the disease mild hyperreflexia in upper limb can be demonstrated but the upper limb involvement is relatively uncommon in HSP. . Hyperreflexia,
Commonly seen in lower limbs due to deficit in corticospinal tract. Axon degeneration maximaly at the distal ends of the corticospinal tracts is the underline pathology.. In early part of the disease mild hyperreflexia in upper limb can be demonstrated but the upper limb involvement is relatively uncommon in HSP. .
Extensor plantar response Disease is typically associated with bilateral extensor plantar responses. This is also a manifestation of corticospinal tract deficit.. Extensor plantar response
Disease is typically associated with bilateral extensor plantar responses. This is also a manifestation of corticospinal tract deficit..
Mild sensory impairment Sensory abnormalities seen in the lower limbs. It is seen among 10%-65% of cases of pure HSP found to have this specially in case of long standing disease.. Axon degeneration found to be occur in lesser extent, at the distal ends of dorsal column fibers.So that mild impairment of vibration sensation seen in the distal lower extremities.. Diminished joint position sense in the extremities of the lower limbs also has been reported.. Mild sensory impairment
Sensory abnormalities seen in the lower limbs. It is seen among 10%-65% of cases of pure HSP found to have this specially in case of long standing disease.. Axon degeneration found to be occur in lesser extent, at the distal ends of dorsal column fibers.So that mild impairment of vibration sensation seen in the distal lower extremities.. Diminished joint position sense in the extremities of the lower limbs also has been reported..
Absent ankle jerks It is an uncommon sign. It occurs due to central axonopathy rather than due to peripheral nerve involvement.. Absent ankle jerks
It is an uncommon sign. It occurs due to central axonopathy rather than due to peripheral nerve involvement..
Muscle wasting Mild muscle wasting is well recognised feature although uncommon in HSP. It is commonly seen in patients who have had the disease for over 10 years. Distal muscles in the lower limbs, usually the small muscles of the foot and tibialis anterior are the muscles that commonly get affected.. Muscle wasting
Mild muscle wasting is well recognised feature although uncommon in HSP. It is commonly seen in patients who have had the disease for over 10 years. Distal muscles in the lower limbs, usually the small muscles of the foot and tibialis anterior are the muscles that commonly get affected..
Dystonia, rigidity and choreoathetosis They are Extrapyramidal signs ,detected in complicated HSP.. Dystonia, rigidity and choreoathetosis
They are Extrapyramidal signs ,detected in complicated HSP..
Retinal changes Optic atrophy and retinal degeneration seen in some patients with complicated HSP.. Retinal changes
Optic atrophy and retinal degeneration seen in some patients with complicated HSP..
Cranial nerve examination findings Normal cranial nerve function and no evidence of corticobulbar tract involvement are the important negative findings on examination.. Cranial nerve examination findings
Normal cranial nerve function and no evidence of corticobulbar tract involvement are the important negative findings on examination..
Peripheral nervous system examination findings Peripheral nerve involving, peripheral neuropathy can be seen in complicated HSP. It has been associated with neuropathic ulcers.. Peripheral nervous system examination findings
Peripheral nerve involving, peripheral neuropathy can be seen in complicated HSP. It has been associated with neuropathic ulcers..
Higher function assessment findings Impairment of higher functions seen in complicated HSP. Defective recent memory, poor perceptual speed, poor visuomotor coordination, impairment of attention and forgetfulness found in affected individuals. But they do not usualy get dysphasia, agnosia, and dyscalculia like features, which suggestive of major cortical involvement.. Higher function assessment findings
Impairment of higher functions seen in complicated HSP. Defective recent memory, poor perceptual speed, poor visuomotor coordination, impairment of attention and forgetfulness found in affected individuals. But they do not usualy get dysphasia, agnosia, and dyscalculia like features, which suggestive of major cortical involvement..
Neurological evaluation of hypertonic bladder Hypertonic urinary bladder is a feature of classic HSP.. Neurological examination should include mental status, reflexes, strength, and sensation including sacral dermatomes to determine whether there are other neurologic conditions contribute to this pathology.. Neurological evaluation of hypertonic bladder
Hypertonic urinary bladder is a feature of classic HSP.. Neurological examination should include mental status, reflexes, strength, and sensation including sacral dermatomes to determine whether there are other neurologic conditions contribute to this pathology..

Investigations - Diagnosis

Fact Explanation
Magnetic resonance imaging (MRI) of the brain and spinal cord Diagnosis often established by clinical history, examination, positive family history rather than going for investigations. Investigations are useful in excluding alternative diagnoses such as cervical/lumbar spondylosis
primary or secondary neoplasms,and
diplegic cerebral palsy etc, but they do not otherwise add a diagnostic certainty to HSP.MRI of the brain and spinal cord are usually normal in HSP patients.,.White matter abnormality as well as thin corpus callosum are MRI brain findings of some patients with complicated HSP..Thinning of the cervical and thoracic spinal cord has been found in some patients with HSP..
Magnetic resonance imaging (MRI) of the brain and spinal cord
Diagnosis often established by clinical history, examination, positive family history rather than going for investigations. Investigations are useful in excluding alternative diagnoses such as cervical/lumbar spondylosis
primary or secondary neoplasms,and
diplegic cerebral palsy etc, but they do not otherwise add a diagnostic certainty to HSP.MRI of the brain and spinal cord are usually normal in HSP patients.,.White matter abnormality as well as thin corpus callosum are MRI brain findings of some patients with complicated HSP..Thinning of the cervical and thoracic spinal cord has been found in some patients with HSP..
Nerve conduction studies Found to be normal in most cases of HSP.. Nerve conduction studies
Found to be normal in most cases of HSP..
EMG Also found to be normal in most cases of pure HSP.. EMG
Also found to be normal in most cases of pure HSP..
CSF analysis It is usually unremarkable in HSP. However increased protein concentrations in complicated families as well as raised homocarnosine concentrations occasionally have been reported.. CSF analysis
It is usually unremarkable in HSP. However increased protein concentrations in complicated families as well as raised homocarnosine concentrations occasionally have been reported..
Molecular genetic testing It has been increasingly available and particularly useful to confirm a clinical diagnosis of HSP. .The most common genes associated with recessive HSP are SPG5A, , SPG11,SPG7, as well as SPG15.2. . However currently it does not include all genes known to cause HSP, so that absence of an identified mutation in a gene known to cause HSP itself does not exclude the diagnosis of HSP.. Molecular genetic testing
It has been increasingly available and particularly useful to confirm a clinical diagnosis of HSP. .The most common genes associated with recessive HSP are SPG5A, , SPG11,SPG7, as well as SPG15.2. . However currently it does not include all genes known to cause HSP, so that absence of an identified mutation in a gene known to cause HSP itself does not exclude the diagnosis of HSP..
Syphilis serology Performed to exclude neurosyphilis. Syphilis serology
Performed to exclude neurosyphilis.
Serum Vitamin B12 level Subacute combined degeneration of the cord due to vitamin B 12 deficiency may resembles HSP. So this investigation is carried out to exclude the presence of subacute combined degeneration of the cord .. Serum Vitamin B12 level
Subacute combined degeneration of the cord due to vitamin B 12 deficiency may resembles HSP. So this investigation is carried out to exclude the presence of subacute combined degeneration of the cord ..

Investigations - Management

Fact Explanation
Full blood count Since some patients have to undergo orthopedic surgeries to release contractures, the baseline investigations such as FBC should be carried out for fitness assessment. . Full blood count
Since some patients have to undergo orthopedic surgeries to release contractures, the baseline investigations such as FBC should be carried out for fitness assessment. .
Fasting blood sugar Performed in individuals who undergo orthopedic surgeries to assess fitness.. Fasting blood sugar
Performed in individuals who undergo orthopedic surgeries to assess fitness..
Prenatal Testing If the disease causing mutation has been identified in an affected family member, this test can be carried out in pregnancies to assess the risk of fetus. It can be performed either testing for this disease/gene or custom prenatal testing.. Prenatal Testing
If the disease causing mutation has been identified in an affected family member, this test can be carried out in pregnancies to assess the risk of fetus. It can be performed either testing for this disease/gene or custom prenatal testing..

Management - Supportive

Fact Explanation
Physiotherapy There is no specific treatment either to prevent or reverse nerve degeneration in HSP. So that current management mainly targeting on reducing symptoms, improving balance and strength, as well as agility.Daily regimen of physical therapy is carried out. It may useful to improve cardiovascular fitness, gait,maintain and improve muscle strength and also to reduce spasticity.. Physiotherapy
There is no specific treatment either to prevent or reverse nerve degeneration in HSP. So that current management mainly targeting on reducing symptoms, improving balance and strength, as well as agility.Daily regimen of physical therapy is carried out. It may useful to improve cardiovascular fitness, gait,maintain and improve muscle strength and also to reduce spasticity..
Occupational therapy Management of these HSP should be multidisciplinary approaches involving several specialties such as physiotherapist as well as occupational therapist etc... Assistive walking devices such as wheelchairs and assistive devices to improve functional gait such as ankle-foot orthotic devices can be provided.. Occupational therapy
Management of these HSP should be multidisciplinary approaches involving several specialties such as physiotherapist as well as occupational therapist etc... Assistive walking devices such as wheelchairs and assistive devices to improve functional gait such as ankle-foot orthotic devices can be provided..
Genetic councelling It is a process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.Since disease is genetically heterogeneous, genetic counselling is a must. Patient and family members should informed about pattern of inheritance, risk of them to get disease, importance of genetic testing as well as related of family planing issues.. Genetic councelling
It is a process of providing individuals and families with information on the nature, inheritance, and implications of genetic disorders to help them make informed medical and personal decisions.Since disease is genetically heterogeneous, genetic counselling is a must. Patient and family members should informed about pattern of inheritance, risk of them to get disease, importance of genetic testing as well as related of family planing issues..
Proper counselling ,patient and family education. Once diagnosis is established, patient should be properly counselled. The should inform about the inheritance pattern of the disease, symptoms, possible complications as well as importance of follow up. Educate the family members that this is a chronic disease and patient always need their helping hand to do their day today works. And make a proper plan for future follow up.. Proper counselling ,patient and family education.
Once diagnosis is established, patient should be properly counselled. The should inform about the inheritance pattern of the disease, symptoms, possible complications as well as importance of follow up. Educate the family members that this is a chronic disease and patient always need their helping hand to do their day today works. And make a proper plan for future follow up..

Management - Specific

Fact Explanation
Baclofen Some patients show increase
functional activity when treated with antispastic drugs such as the GABA agonist baclofen or newer
alternatives.Oral or intrathecal Baclofen can be used. Other drugs include tizanidine and dantrolene which also reduce muscle spasticity. ,.
Baclofen
Some patients show increase
functional activity when treated with antispastic drugs such as the GABA agonist baclofen or newer
alternatives.Oral or intrathecal Baclofen can be used. Other drugs include tizanidine and dantrolene which also reduce muscle spasticity. ,.
Botox injections Intramuscular botulinum toxinfound to be improve function in selected group of patients.. It is also useful in reducing muscle spasticity.. Botox injections
Intramuscular botulinum toxinfound to be improve function in selected group of patients.. It is also useful in reducing muscle spasticity..
Oxybutynin It is an antimuscarinic drug. It is a tertiary amine that has anticholinergic, spasmolytic,as well as local anesthetic properties. It causes relaxation of the smooth muscle by acting as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors on the detrusor muscle of the bladder..It is reduce urinary urgency..The frequency and severity of the side effects are dose dependent and untreated narrow-angle glaucoma urinary retention as well as severely decreased gastric motility conditions considered as contraindications to oxybutynin.. Oxybutynin
It is an antimuscarinic drug. It is a tertiary amine that has anticholinergic, spasmolytic,as well as local anesthetic properties. It causes relaxation of the smooth muscle by acting as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors on the detrusor muscle of the bladder..It is reduce urinary urgency..The frequency and severity of the side effects are dose dependent and untreated narrow-angle glaucoma urinary retention as well as severely decreased gastric motility conditions considered as contraindications to oxybutynin..
Orthopaedic surgery Performed to release of contractures
and tenotomie. But they may rarely have a role..
Orthopaedic surgery
Performed to release of contractures
and tenotomie. But they may rarely have a role..

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