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Acquired Neuropathies

Peripheral neuropathies constitute a heterogeneous group of disorders affecting the peripheral nervous system, impairing the function of the nerves that connect the central nervous system to muscles, skin, and internal organs. They are classically divided into acquired forms, with an estimated prevalence between 2% and 8% of the general population, and genetic/hereditary forms, the most common variants of which reach an incidence of approximately 1 in 2,500 inhabitants.

From an etiopathogenetic perspective, acquired neuropathies arise from multiple causes:

  • Metabolic: (Diabetes mellitus represents the most frequent cause overall).

  • Autoimmune: (Such as Guillain-Barré syndrome and CIDP).

  • Infectious: (HIV, borreliosis/Lyme disease, leprosy).

  • Toxic: (Alcohol, chemotherapeutic agents, heavy metals).

  • Deficiency-related: (Particularly deficiencies in vitamins B12, B1, and B6).

Neuropathies present a heterogeneous clinical spectrum depending on the type and distribution of the involved fibers:

Motor Manifestations

  • Muscle weakness: Progressive, often initially distal and later proximal.

  • Muscle atrophy: Loss of muscle mass, prominent in the intrinsic muscles of the hands and feet.

  • Cramps and fasciculations: Involuntary contractions, nocturnal spasms.

  • Functional difficulties: Difficulty gripping objects, walking, or climbing stairs.

Sensory Manifestations

  • Positive sensory disturbances: Tingling, numbness, paresthesias.

  • Neuropathic pain: Burning, stabbing, or electric shock-like sensations.

  • Sensory loss: Loss of touch, vibration, and position sense (stocking-and-glove distribution).

  • Allodynia: Pain from light touch; hyperalgesia.

Autonomic Manifestations

  • Sweating alterations: Anhidrosis (lack of sweating) or hyperhidrosis.

  • Gastrointestinal dysfunction: Gastroparesis, diarrhea, constipation.

  • Cardiovascular: Orthostatic hypotension, arrhythmias.

  • Urogenital: Urinary retention, incontinence, erectile dysfunction.

Clinical Assessment and Diagnostic Strategy

  • Clinical Evaluation: Detailed family history (essential when hereditary forms are suspected), comprehensive neurological examination (strength, sensation, reflexes), and identification of the deficit distribution pattern.

  • Electrophysiology:

    • Electroneurography (NCS): Nerve conduction velocity, identification of demyelinating or axonal patterns.

    • Electromyography (EMG): Assessment of axonal damage and reinnervation.

  • Laboratory Tests: Diabetes screening (blood glucose, HbA1c), thyroid function (TSH, fT3, fT4), vitamins (B12, B1, B6, folates), immunoelectrophoresis (monoclonal proteins), and specific antibodies (anti-MAG, anti-GM1, anti-gangliosides).

  • Specialized Imaging: * Spinal MRI: To exclude radiculopathies.

    • Nerve Ultrasound: Detection of thickening and structural alterations.

    • Muscle and Nerve MRI: Specific atrophy patterns.

  • Invasive Tests: * Sural Nerve Biopsy: Reserved for selected cases; differential diagnosis in suspected storage diseases or vasculitis.

    • Lumbar Puncture: Analysis of protein levels, cell count, and oligoclonal bands.

  • Rating Scales: CMT Neuropathy Score (CMTNS), Overall Disability Sum Score (ODSS), Quality of Life (SF-36), and neuropathic pain scales (DN4, NPSI).

Diagnostic Strategy Flowchart

Clinical Suspicion → Neurophysiology → Laboratory Investigations → Genetic Testing (if hereditary suspected) → Specialized Examinations

Available therapies

Acquired Neuropathies – Etiological Therapy

Metabolic Forms:

  • Diabetes: Optimal glycemic control (HbA1c <7%), metformin, insulin.

  • Hypothyroidism: Levothyroxine, TSH monitoring.

  • Uremia: Dialysis optimization, kidney transplant.

Deficiency Supplementation:

  • Vitamin B12: Cyanocobalamin IM 1,000 μg, followed by oral maintenance.

  • Thiamine (B1): 100-300 mg/day for severe deficiency forms.

  • Folates: 5-15 mg/day, in association with B12.

Immunosuppressive Therapies:

  • Corticosteroids: Prednisolone 1 mg/kg for CIDP, slow tapering.

  • Intravenous Immunoglobulins (IVIG): 2 g/kg over 5 days for Guillain-Barré/CIDP.

  • Plasmapheresis: 4-6 sessions for severe acute cases.

  • Rituximab: Anti-MAG neuropathies, 375 mg/m² weekly x4.

  • Mycophenolate: 1-3 g/day for CIDP maintenance.

Neuropathic Pain Therapy:

  • First-line: Gabapentin 900-3,600 mg/day, pregabalin 150-600 mg/day.

  • Antidepressants: Duloxetine 60-120 mg/day (diabetic), amitriptyline 25-150 mg/day.

  • Anticonvulsants: Carbamazepine for trigeminal neuralgia, lamotrigine.

  • Opioids: Tramadol, oxycodone for selected refractory cases.

Genetic Neuropathies – Supportive Therapies

Physiotherapy and Rehabilitation:

  • Strengthening exercises, stretching, and prevention of retractions/contractures.

  • Orthotics: AFO (Ankle-Foot Orthosis) for drop-foot, insoles for pes cavus, hand braces.

  • Walking Aids: Forearm crutches (Canadian crutches), walkers, wheelchairs.

  • Occupational Therapy: Environmental adaptations, gripping aids.

Orthopedic Management:

  • Pes Cavus (High Arch): Insoles, arthrodesis, tendon transfers.

  • Scoliosis: Bracing, surgical stabilization.

  • Hand Deformities: Functional surgery, tenodesis.

Emerging Experimental Therapies:

  • Gene Therapies: Viral vectors for correcting genetic defects.

  • Expression Modulators: Antisense oligonucleotides (ASOs).

  • Regenerative Medicine: Stem cells, growth factors.

Research in progress

Active Clinical Trials

  • Innovative CIDP Therapies: New immunosuppressants, anti-FcRn (neonatal Fc receptor) agents, anti-complement therapies, and monoclonal antibodies.

  • Neuropathy Biomarkers: Early identification of disease progression and therapeutic response.

  • CMT Gene Therapies: Experimental protocols for gene correction.

  • Neuropathic Pain: Multimodal strategies and innovative pharmaceuticals.

Translational Research

  • Cellular Models: Patient-specific iPSCs (induced Pluripotent Stem Cells) for pharmacological screening.

  • Cerebrospinal Fluid (CSF) Biomarkers: Neurofilaments and specific proteins.

  • Innovative Imaging: High-resolution MRI of the nerves (MR Neurography).

International Collaborations

  • Hereditary Neuropathy Network: International registries and coordinated trials.

  • CIDP Consortium: Standardized protocols and shared biomarkers.

Acquired Neuropathies at the Policlinico

  • Dedicated Outpatient Pathway: Neuropathy Clinic (Ambulatorio Neuropatie S05 NEU), bookable via the regional toll-free number.

  • Availability of Key Diagnostic Methods:

    • Blood tests including antibody screening.

    • Lumbar puncture (spinal tap).

    • Neurophysiology (EMG/NCS).

    • Sural nerve biopsy.

    • MRI of the spine and plexuses.

  • Expertise in Conventional Drug Treatments: Extensive experience with standard therapies.

  • Access to Experimental Trials: Opportunity for inclusion in pharmacological trials; specifically, studies involving anti-complement and anti-FcRn agents for CIDP are currently being launched.

Reference laboratory

Contacts and informations

Email: malattieneuromuscolari@policlinico.mi.it

Associazioni pazienti:

  • CIDP Italia:  Supporto specifico CIDP
  • UILDM:  Tel. 049 8021001
  • ASNP: Associazione Studio Neuropatie Periferiche

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