French guidelines for the diagnosis and management of pure hereditary spastic paraplegia

Introduction

Hereditary spastic paraplegia (HSP) describes a group of rare genetic neurological diseases characterized by a common clinical presentation made of progressive motor weakness and spasticity of the lower limbs. The global prevalence is estimated at 3.6 individuals per 100,000 inhabitants.

Clinical

The age of onset of first symptoms, the severity and the rate of progression are highly variable between different HSP subtypes, ranging from juvenile forms that present in the first years of life, to the later-onset forms, sometimes presenting after the age of 60. The medical history most often reveals an insidious onset of gait disturbances due to lower limb stiffness. The clinical examination reveals the key symptoms of HSP: pyramidal signs of the lower limbs with motor weakness predominantly involving the proximal muscles. As the condition progresses, moderate upper limb involvement as well as bladder and sphincter disorders may be present. When associated with other neurological or extra-neurological signs such as cerebellar ataxia, optic neuropathy, cardiomyopathy, or intellectual disability, HSP is referred to as “complex”. This is in contrast to the pure forms of HSP, where the pyramidal syndrome of the lower limbs occurs in isolation, which will be treated here.

Physiopathology

HSPs are a genetically heterogeneous group of disorders involving numerous distinct molecular pathways. However, regardless of the initial mechanism, they share a common pathophysiology characterized by primary first motor-neuron involvement. Lesions tend to predominate in the spinal cord, following a phenomenon of retrograde degeneration (“dying-back”) of the corticospinal tract.

Diagnosis and genetic counseling

The diagnostic approach will first aim to eliminate all non-genetic acquired forms of spastic paraplegia as well as other various differential diagnoses. More than 100 genes and disorders are grouped under the term HSP, with age of onset, disease progression and clinical presentation being highly variable. Pure forms of HSP are primarily inherited in an autosomal dominant or recessive manner. Genetic counseling for the patient and their family is ideally provided by a clinical geneticist once the precise molecular diagnosis has been obtained.

Management and care

The management of pure HSP is multidisciplinary. Its goal is to prevent complications and to propose symptomatic treatment at all stages of the disease. It is primarily based on motor rehabilitation through physiotherapy and physical activity. Psychological support should be offered from the moment the diagnosis is announced and throughout the follow-up. Multidisciplinary follow-up is coordinated by the primary care physician, in consultation with the expert pediatric neurologist/neurologist or neurogeneticist, and equally involves a physical medicine and rehabilitation physician and paramedical professionals (such as physiotherapists, social workers, occupational therapists, and psychologists).