Serotonin syndrome vs neuroleptic malignant syndrome — distinguishing these drug-induced emergencies is one of the highest-value clinical differentials in pharmacology. Both cause hyperthermia, altered consciousness, and movement abnormalities — but the causative drugs, mechanisms, and specific clinical features differ critically. Serotonin syndrome: excess serotonergic activity (SSRIs + MAOIs, tramadol, fentanyl, triptans, lithium, linezolid, MDMA). Clinical: hyperreflexia + clonus (the pathognomonic feature — spontaneous rhythmic oscillations at the ankle or knee) + agitation + myoclonus + tremor. Onset: hours. NMS: dopamine blockade (antipsychotics, metoclopramide). Clinical: lead-pipe rigidity (uniform resistance throughout passive limb movement) + bradykinesia + markedly elevated CK + autonomic instability. Onset: days-weeks. The bedside test: elicit ankle clonus (dorsiflex the foot briskly and sustain the dorsiflexion — sustained clonus = SS). Test lead-pipe rigidity (passively flex/extend wrist — uniform ratchet resistance throughout range = NMS, not just at initiation). Both are treated by stopping the causative drug and hospital admission, with hospital-led supportive care; specialists may consider cyproheptadine (SS) or bromocriptine/dantrolene (NMS). Wilson's disease is the diagnosis most commonly missed in young adults with tremor — diagnosis is often delayed. The disease is treatable with specialist-initiated copper chelation or zinc if caught early; missed diagnosis causes irreversible hepatic and neurological damage.

Alcohol response is neither sufficiently sensitive nor specific to diagnose essential tremor and should not be used as a diagnostic or therapeutic trial because of the risk of misuse and dependence. Some people with tremor drink to reduce it — ask non-judgementally about alcohol use, assess dependence using a validated local pathway and offer support where indicated.

Wilson's disease serology interpretation: caeruloplasmin is the copper-carrying protein synthesised in the liver — it is low in Wilson's disease because the mutant ATP7B protein cannot incorporate copper into caeruloplasmin before secretion, causing both low caeruloplasmin and free copper accumulation in tissues. However, caeruloplasmin is an acute-phase reactant — it can be falsely normal or elevated during inflammation, pregnancy, or OCP use. Low caeruloplasmin also occurs for other reasons, so it is not diagnostic alone; testing is specialist-led. 24-hour urinary copper is a specialist test interpreted with other results. The Kayser-Fleischer ring is a highly specific clinical sign — a golden-brown arc at the periphery of the cornea on slit-lamp examination, usually present in neurological Wilson's. GPs do not need a slit lamp to suggest this diagnosis — request ophthalmology review for slit-lamp examination in any young patient with unexplained neurological symptoms + liver disease. Functional tremor (functional movement disorder, FMD) is increasingly recognised as a common diagnosis in neurology clinics — it is a common reason for neurology referral with tremor. The traditional view that functional tremors are 'psychosomatic' or 'not real' has been superseded by neuroimaging evidence of genuine abnormal motor control mechanisms. GPs should refer to neurology with this diagnosis in mind rather than labelling patients as 'anxious' or 'seeking attention'.

The re-emergent tremor of Parkinson's disease is one of the most clinically useful diagnostic findings — when a patient with PD holds their arms outstretched, the resting tremor (which is present at rest and suppressed by initiating movement) initially disappears. However, after 5–15 seconds of sustained posture, the tremor re-emerges at the same frequency as the resting tremor. This re-emergent postural tremor of PD is distinct from the immediately-appearing postural tremor of essential tremor and is a key diagnostic discriminator. GPs who observe this re-emergent pattern during posture-hold testing should record it explicitly — it supports a Parkinson's diagnosis and justifies prompt neurology referral. NICE NG71 (Parkinson's disease, 2017) advises referring suspected Parkinson's quickly to a specialist for diagnosis, because distinguishing PD from Parkinson's-plus syndromes (MSA, PSP) is a specialist assessment. Do not delay referral while waiting for imaging. Initiation of levodopa or other Parkinson's medication should follow local neurology/shared-care arrangements; NICE bases treatment decisions on the effect of motor symptoms on quality of life, so if a long wait is causing significant disability, seek specialist advice.

Specialist diagnosis before committing to long-term Parkinson's medication protects patients from two specific harms: (1) Starting levodopa in a patient who has MSA or PSP — both of which initially resemble PD but respond poorly to levodopa and have worse prognosis. Initiating levodopa empirically in MSA gives a false reassurance that the patient has PD, delays the correct diagnosis, and exposes the patient to medication that will not significantly help them. (2) Missing an atypical presentation of a tumour, vascular disease, or drug-induced parkinsonism that requires different investigation and management. The specialist assessment typically takes 30–60 minutes and includes: careful history (onset symmetry, falls early in course, eye movement abnormalities for PSP), examination (pull test for postural instability, downward gaze palsy for PSP, cerebellar signs for MSA), and often DaTSCAN (dopamine transporter SPECT scan) to confirm dopaminergic deficit. The DaTSCAN differentiates Parkinson's from essential tremor (both have clinical tremor but only PD has reduced striatal dopamine transporter uptake) but cannot distinguish PD from other parkinsonian syndromes.

Propranolol helps many people with essential tremor enough to improve daily activities (holding a cup, writing, eating). Those who do not respond or cannot tolerate it may be offered primidone — the two drugs work via different mechanisms and a non-responder to one may respond to the other. Primidone is converted to phenobarbitone in the liver, which enhances GABA-A-mediated inhibition; propranolol works via beta-2 receptor antagonism reducing peripheral tremorgenic signalling. Combining both at lower doses can provide additive benefit with fewer side effects than high-dose monotherapy. The performance anxiety tremor use case (single 40 mg propranolol before a high-stakes event) is well-evidenced in musicians, surgeons, public speakers, and examinees, and can be an appropriate prescribing decision after checking contraindications, with review rather than unreviewed repeat prescriptions.

Focused ultrasound thalamotomy (FUS-T) is a transformative non-invasive procedure for essential tremor, assessed in 2018 (NICE HTG474, formerly IPG617: special arrangements for clinical governance, consent and audit or research) and represents a major advance for patients with severe disabling unilateral ET who have failed or cannot tolerate propranolol and primidone. The procedure uses 1024 ultrasound transducers focused through the intact skull onto the VIM nucleus of the thalamus — the focused convergence of sound waves creates precise tissue heating at the target, ablating the thalamic oscillator circuit responsible for ET without any incision or implanted hardware. Treatment is unilateral (usually the dominant hand) and outcomes vary. The limitation is that bilateral treatment carries significant risks of dysarthria and gait ataxia, so most patients are treated unilaterally. GPs should be aware of FUS-T as a specialist-assessed option for selected treatment-resistant ET; availability is limited.

People with Parkinson's disease usually need to notify the DVLA — advise them to check the current DVLA medical standards. The DVLA assesses fitness to drive individually and makes the final decision. The GP's obligation is to: (1) advise the patient of this requirement at or shortly after diagnosis; (2) document in the clinical record that this advice was given; (3) advise the patient not to drive if they develop symptoms that affect driving safety (significant tremor, dyskinesias, cognitive impairment, excessive daytime sleepiness from dopaminergic medications) and to notify the DVLA again if their condition deteriorates. Notifying the DVLA is the licence holder's legal duty. If a patient continues to drive when advised not to, GMC confidentiality guidance allows the doctor to inform the DVLA after telling the patient.

The lithium toxicity-tremor connection is an important prescribing safety point — lithium has a narrow therapeutic range (0.6–1.0 mmol/L for maintenance), and tremor is one of the earliest signs of both therapeutic and toxic levels. A fine postural hand tremor at therapeutic levels is expected and common. However, worsening tremor should always prompt a serum lithium level check — a level above 1.5 mmol/L indicates significant toxicity, with neurological features (coarse tremor, ataxia, confusion, seizures) becoming more prominent above 2.0 mmol/L. The most common causes of lithium toxicity in primary care are: dehydration (vomiting, diarrhoea, hot weather — reduced renal clearance), new prescription of NSAIDs or ACE inhibitors (both reduce renal lithium clearance), sodium-restricted diets (reduced sodium → compensatory lithium retention), and use of diuretics. Any patient on lithium who presents with worsening tremor should have a lithium level checked that day — not at next routine monitoring date.