Hereditary transthyretin amyloidosis arises from misfolding of transthyretin and deposition of amyloid fibrils in nerves and organs. In carriers of V122I and T60A variants, neuropathy may be late-onset and mixed with cardiac involvement (V122I) or present as a length-dependent sensorimotor and autonomic neuropathy with variable cardiac features (T60A). Small-fiber pain, numbness, gait imbalance, orthostatic intolerance, and gastrointestinal dysautonomia are common and can erode independence.

Hereditary transthyretin amyloidosis management now includes RNA interference therapies that silence hepatic TTR, aiming to reduce the supply of amyloidogenic protein and mitigate ongoing axonal injury. Among these, patisiran has demonstrated clinically meaningful effects on neuropathy impairment and quality of life in hATTR. In V122I and T60A populations specifically, pragmatic signals suggest neuropathy can stabilize and, in some patients, improve over the first 6 to 12 months, aligning with a time course that clinicians can use to structure follow-up. The following implementation guidance is designed to help teams operationalize these insights in everyday care.

Identify clinical phenotypes early. V122I is frequently associated with cardiomyopathy and later, milder neuropathy that may be underrecognized; T60A often presents with mixed cardiac and neurologic features and a classical length-dependent pattern. Look for red flags: distal burning pain, numbness, temperature loss, progressive gait instability, falls, orthostasis, diarrhea/constipation cycles, erectile dysfunction, unexplained weight loss, and a history of bilateral carpal tunnel release. In both variants, symptom detection often lags behind pathology; a low threshold for neurologic confirmation helps start therapy before irreversible axonal loss.

• Confirm diagnosis with pathogenic variant testing (document V122I or T60A), clinical phenotype, and exclusion of mimics (e.g., diabetes, B12 deficiency, CIDP, alcohol-related neuropathy).
• Baseline neurological assessment should quantify function to anchor expectations: incorporate a structured impairment score (e.g., NIS or mNIS+7 if available), vibration pin thresholds, ankle reflexes, and simple functional measures (10-m walk, timed up-and-go, grip strength).
• Autonomic profile using orthostatic vitals, symptom scales (e.g., gastrointestinal, sudomotor), and, if available, heart rate variability or QSART helps capture the non-motor burden.
• Nerve conduction studies (NCS) provide objective large-fiber benchmarks. If small-fiber symptoms dominate, consider quantitative sensory testing where accessible.
• Cardiac status is essential, especially in V122I: NT-proBNP, ECG, echocardiography (wall thickness, diastolic function), and rhythm evaluation inform safety, functional goals, and rehab plans.

Therapy initiation. When polyneuropathy is symptomatic or documented by objective measures, initiating patisiran can plausibly stabilize or improve impairment. In more advanced axonal loss, the realistic goal often shifts toward slowing decline and maintaining independence. Set expectations that meaningful changes typically emerge by 6 to 12 months, with earlier signals in pain, autonomic symptoms, and gait steadiness for some patients.

Counseling on goals. Frame outcomes around function: fewer falls, improved walking endurance, reduced neuropathic pain, better gastrointestinal regularity, and improved hand dexterity. Be transparent: regeneration of long axons is limited; however, halting ongoing damage and relieving toxic milieu can translate to stabilization and selective improvements. For V122I, emphasize concurrent cardiology management because cardiac output and conduction status can amplify or mask neurologic gains.

Define a standard follow-up cadence. A structured schedule supports early detection of response and complications.

• Baseline: neurologic exam and functional measures; NCS if feasible; autonomic symptom inventory; fall risk assessment; cardiac testing; nutritional evaluation (including vitamin A status and general micronutrients).
• Month 3: focused neurologic exam; patient-reported outcomes (pain, orthostasis, GI diary); check for infusion reactions; ensure vitamin A supplementation adherence; reassess falls and gait.
• Month 6: repeat functional measures; consider NCS if change is unclear; review autonomic symptoms; reassess cardiac status if symptomatic changes occur; adjust PT/OT and orthotic needs.
• Month 12: comprehensive reassessment mirroring baseline to judge trajectory; document maintenance, improvement, or progression across domains.

Select practical measures you can repeat reliably. Tertiary centers may use composite scores such as mNIS+7; however, many clinics can track:

• Neurologic exam: ankle dorsiflexion strength, vibration at great toes, ankle reflexes, pinprick thresholds.
• Function: 10-meter walk speed, timed up-and-go, 6-minute walk distance when cardiopulmonary status permits, grip strength, buttoning or peg tests for dexterity.
• Falls and gait: monthly falls log, use of assistive devices, physical therapy notes on balance and endurance.
• Autonomic burden: orthostatic vitals (supine and 1–3 minutes standing), bowel movement frequency, constipation/diarrhea episodes, urinary symptoms, erectile dysfunction responses, sweating changes, weight trends.
• Quality of life: a neuropathy-specific questionnaire to capture symptom impact on daily living.

Coordinate multidisciplinary care. V122I and T60A often require oversight by neurology, cardiology, genetics, and rehabilitation. Shared information reduces conflicting signals. For example, a patient with improved distal strength but worsening exertional capacity may be limited by diastolic dysfunction; conversely, improved heart rate control can unmask neurologic progress. Regular case reviews (e.g., every 6 months) align goals and therapy adjustments.

Rehabilitation and fall prevention. Early physical therapy targeting ankle dorsiflexion strength, proprioception, and dynamic balance reduces falls and supports gait efficiency. Occupational therapy can address hand dexterity, footwear and orthotic optimization, and home safety. In advanced sensory loss, consider ankle-foot orthoses for foot drop and cane or walker training. For autonomic symptoms, nonpharmacologic measures (hydration, salt if appropriate, compression garments) and pharmacologic agents can be layered.

Nutritional support. Weight loss from dysautonomia or early satiety is common. Registered dietitian input helps maintain caloric and protein targets and ensures vitamin A supplementation, which is recommended during patisiran therapy due to lowering of circulating retinol-binding protein. Monitor for symptoms of hypovitaminosis A (night vision difficulties, dry eyes) and adjust supplementation accordingly.

Cardiac co-management. For V122I, cardiomyopathy often dominates functional capacity and survival. Echocardiography, rhythm surveillance, and natriuretic peptide trends guide diuretic titration, rhythm control, and device considerations. While neurologic outcomes may stabilize with patisiran, concurrent cardiac trajectory affects perceived benefit. Ensure that rehabilitation plans respect hemodynamic limits and that medication changes (e.g., beta-blockers) are communicated across the team.

Medication reconciliation and polypharmacy. Avoid duplicative therapies and unintended interactions. If disease-modifying cardiac therapies are used, document the rationale, expected effects, and timelines to prevent misattribution of neurologic changes. Keep pain regimens balanced to support function while minimizing side effects that can worsen dizziness or gait instability.

Set expectations transparently. For both V122I and T60A, the most consistent pattern in practice is stabilization with potential for selective improvements, particularly when therapy begins earlier in the course. Counsel that improvement may be gradual and that steady work in physical therapy, orthostatic countermeasures, and nutrition enhances gains. Revisit goals at 3, 6, and 12 months and adjust the care plan accordingly.

Safety monitoring and mitigation. Patisiran is administered as an intravenous infusion. Premedication is typically used to reduce infusion-related reactions. Educate patients about possible symptoms during or shortly after infusion, such as flushing, dyspnea, chest discomfort, or back pain, and the value of rate adjustments and supportive measures if reactions occur. Reinforce adherence to vitamin A supplementation and prompt reporting of night vision changes. Track general tolerability, including fatigue or headache, and coordinate with infusion services to troubleshoot access issues.

Infusion logistics and access. Align the infusion schedule with patients daily routines, transportation, and caregiver availability. Explore options for infusion center versus home infusion based on local availability and payer policies. Provide clear checklists for pre-infusion review (symptoms, vitals, recent infections, intercurrent illnesses) and post-infusion monitoring. Ensure communication pathways so that adverse events reach the prescribing clinician quickly.

Communication scripts for clinician-patient discussions. Plain-language summaries can reduce anxiety and support adherence:

• Mechanism: This medicine lowers the liver production of transthyretin, which contributes to nerve damage; by reducing the source, we aim to protect the nerves from further injury.
• Timing: Many patients notice change over 6 to 12 months; early signs can be steadier walking, fewer falls, or less pain.
• Goals: We expect to stabilize and sometimes improve nerve function; we will measure progress using strength tests, walking speed, and daily function checklists.
• Teamwork: Because your heart and nerves can both be affected, our neurology and cardiology teams coordinate to keep your plan safe and effective.

Variant-specific considerations.

• V122I: Commonly later-onset with predominant cardiomyopathy. Neuropathy may be subtle; prioritize small-fiber symptom screening and objective gait measures. Improvements in neuropathic pain and balance may occur even if large-fiber conduction changes are modest. Cardiac status can overshadow perceived neurologic benefit, so pair neurologic milestones with cardiology metrics when counseling.
• T60A: Often mixed phenotype. Length-dependent sensory loss and autonomic dysfunction can be prominent. Earlier initiation may yield clearer functional gains; track constipation/diarrhea cycles, orthostatic symptoms, and distal strength to capture meaningful improvements.

When response is unclear. If function appears unchanged at 6 months, confirm adherence and reassess confounders: new medications causing neuropathy-like symptoms (e.g., chemotherapeutics), poorly controlled diabetes, vitamin deficiencies, spinal stenosis, or worsening cardiac output. Consider repeating NCS or adding small-fiber assessments. Stabilization without improvement may still reflect therapeutic benefit compared with the expected natural history of progression; frame discussions accordingly.

Escalation and referrals. Persistent falls, rapid deterioration, severe autonomic neuropathy, or complex pain warrant referral to specialized amyloidosis centers for advanced testing, rehabilitation design, and comprehensive management. Social work and genetic counseling support family screening, caregiver burden, and advance care planning.

Documentation tips for payers and continuity. Link each visit to measurable outcomes: walk speed, falls count, orthostatic change, hand function, patient-reported pain and GI scores, and any assistive device adjustments. Describe how therapy supports independence and safety (e.g., returning to household activities, reduced falls). Well-structured notes facilitate authorization renewals and team coordination.

Practical checklist for the clinic.

• Confirm variant (V122I or T60A), phenotype, and baseline neurologic and cardiac status.
• Start vitamin A supplementation and intake counseling; educate about night vision symptoms.
• Establish trackable measures: 10-m walk, timed up-and-go, grip strength, orthostatic vitals, falls diary, neuropathic pain score, and GI symptom log.
• Schedule follow-up at 3, 6, and 12 months with predefined reassessment panels.
• Engage PT/OT early; review home safety and assistive devices.
• Coordinate with cardiology for V122I and mixed phenotypes; align rehab intensity with hemodynamics.
• Plan for infusion logistics; set expectations for premedication and potential infusion reactions.
• Reinforce adherence and address barriers (transportation, caregiver support, cost navigation).

What to tell patients about the road ahead. With treatment, many patients see neuropathy stabilize and some improve, especially when therapy begins earlier. Progress is typically incremental; small wins add up: steadier walking, better hand control, fewer dizzy spells, more confidence. The care team will keep tracking your measurable changes so we can adjust the plan and help you preserve independence.

Summary for practice. For V122I and T60A hATTR, a structured approach to patisiran therapy focuses on timely initiation, reproducible measurement, and cardio-neuro coordination. Expectation-setting around stabilization with potential improvements over 6 to 12 months is realistic. Consistent monitoring of function and autonomic symptoms, proactive rehabilitation, and infusion logistics planning can translate evidence into outcomes that matter to patients.