Category Archives: Neurology

Lyme Disease

Cardiology, General paediatrics, Infectious disease, Microbiology, Neurology, Rheumatology

Borrelia (spirochaete) infection, spread by ticks (Ixodes), common in localized areas of Europe and North America (forest environments).

Differential includes possible co-infection from other tick born organisms viz anaplasmosis, or babesiosis.

Vaccine available if likely to be at risk.

Clinical

Infection occurs a minimum of 48 hours after bite!

Skin – Erythema migrans is the classic skin lesion, a spreading ring usually at the site of the bite but can be multiple and at different sites.  Typically not hot, itchy or painful. Takes a while for central clearing to develop. Develops over 1-4 weeks (from 3 days to 3 months!), can last months.  Looks like erythema multiforme, but time scale different.  Insect bite hypersensitivity/superinfection looks similar but usually hot, itchy and/or painful, and develops/recedes within 48 hours!

Lyme lymphocytoma is a painless bluish red nodule or plaque, especially on the ear but also reported on the nipple and scrotum.  More common in children.  May persist for months, can precede other features.  Acrodermatitis chronica atrophicans (ACA) is almost exclusively seen in adults, predominantly women, and is an eruption with chronic, progressive red or bluish-red lesions, usually on the extensor surfaces, with later atrophic, fibroid or sclerodermic changes.

Consider Lyme as possible (but unlikely) cause for:

  • fever and sweats
  • swollen glands
  • malaise
  • fatigue
  • neck pain or stiffness
  • migratory joint or muscle aches and pain
  • cognitive impairment, such as memory problems and difficulty concentrating (sometimes described as ‘brain fog’)
  • headache
  • paraesthesia

Arthritis – uncommon, presents as recurrent inflammation of 1 or more large joints, usually the knee. Swelling can be disproportionate to pain.  Can become more persistent – in a minority, despite treatment, inflammation becomes chronic (presumably immune-mediated).

Carditis occurs rarely, and almost always with other clinical features.  Usually partial heart block, but can be complete, usually resolves within a week.

Neurological – isolated facial palsy, meningitis, other cranial nerve palsies, meningoencophalitis, polyradiculopathy.  There is a small proportion of children who can present with non-specific headache, fatigue, neck pain without clear neurological signs (and also the rare case of raised intracranial pressure).

Other rare disease manifestations include uveitis, iridocyclitis and keratitis.

Diagnosis

For erythema migrans, clinical diagnosis is adequate, and antibodies only positive in 30-70% anyway!

Use a combination of clinical presentation and laboratory testing to guide diagnosis and treatment in people without erythema migrans. Do not rule out diagnosis if tests are negative but there is high clinical suspicion of Lyme disease.

  • Offer an enzyme-linked immunosorbent assay (ELISA) test for Lyme disease – consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion. (Test for both IgM and IgG antibodies)
  • If the ELISA is positive or equivocal, perform an immunoblot test for Lyme disease (again, consider starting treatment with antibiotics while waiting for the results if there is a high clinical suspicion). [Western blot increases specificity, but cut offs (for both serology and Western blot) can be an issue, with potential false positives for other acute infections and autoimmune conditions.  Definitely needs to be an approved lab…]
  • If ELISA negative and the person still has symptoms, review their history and symptoms, and think about the possibility of an alternative diagnosis.  If tested within 4 weeks from symptom onset, repeat the ELISA 4 to 6 weeks after the first test.
  • If Lyme disease is still suspected in people with a negative ELISA who have had symptoms for 12 weeks or more, perform an immunoblot test.  If negative, consider synovial fluid aspirate/biopsy, or lumbar puncture [PCR – culture is difficult – or CSF antibodies for neuroborreliosis; consider for isolated facial palsy]
  • If immunoblot negative and symptoms resolved, no treatment is required.

For early neuroborreliosis, antibodies 80% sensitive, rises to virtually 100% for late or ACA.

Early antibiotic treatment is also believed to potentially block antibody production.

Antibodies can then persist for months or even years after successful treatment of the infection, so repeat testing is not useful for monitoring treatment success.

First line ELISA test can have false positives for other spirochaetes, glandular fever and autoimmune conditions.

The idea that there are seronegative “chronic Lyme” cases has little evidence to support it, with only 2 possible cases reported (ACA and arthritis, not neuro).

NICE says “Discuss the diagnosis and management of Lyme disease in children and young people under 18 years with a specialist, unless they have a single erythema migrans lesion and no other symptoms. Choose a specialist appropriate for the child or young person’s symptoms dependent on availability, for example, a paediatrician, paediatric infectious disease specialist or a paediatric neurologist.”

Treatment [check NICE]

The most commonly recommended first-line treatments for different stages of Lyme borreliosis in Europe are:

  • Erythema migrans/borrelial lymphocytoma:  10-14 days Doxycycline if 9yr+ (initially 5 mg/kg in 2 divided doses on day 1, then 2.5 mg/kg daily in 1–2 divided doses, max dose 200mg, for a total of 21 days, option for higher dosing) – 10 days courses of doxy effective in US trials.  Else Amoxicillin 50mg/kg/d, max 500mg TDS (10-14 days)[BNFc says 30mg/kg/d, max 1g, TDS for 21 days].  Don’t delay treatment pending test results.  Scandinavia use 10 days Pen V (100mg/kg/d, max 1000mg TDS). BNFc says Azithromycin as alternative.
  • Isolated facial palsy: 14 days Oral doxycycline  – else as above.  Doesn’t probably help resolution but may prevent later complications.
  • Meningitis/radiculopathy: PO Doxycycline or IV Ceftriaxone  50-100mg/kg/d, max 2g daily (14-21 days). [BNFc talks about CNS disease separate from cranial/peripheral nerves]
  • Encephalitis, myelitis: Ceftriaxone (14 days)
  • Lyme arthritis: Doxycycline (28 days) else Amoxicllin (21-28 days)
  • Carditis: Ceftriaxone during pacing, else PO doxycycline (14 days)

Ceftriaxone is the most commonly preferred parenteral agent, with once-daily dosing facilitating outpatient treatment. Recent prospective studies have shown that oral doxycycline is noninferior to ceftriaxone in neuroborreliosis, and it is now recommended in Europe for the treatment of acute facial palsy (FP), meningitis and radiculoneuritis. Ceftriaxone currently remains the preferred choice for children with other presentations of neuroborreliosis and for those with contraindications to doxycycline.

Several recent EM treatment studies have incorporated noninfected control groups. Excellent responses were seen, with resolution of rash within 7–14 days. Nonspecific symptoms including headache, myalgia, arthralgia, fatigue and parasthesias were no more common in cases than controls at 6-month follow up.

[position statement by the British Infection Association, J Inf 2011;62:329]

[Pediatric Infectious Disease Journal Volume 33(4), April 2014, p 407–409]  

Head injury

Child protection, General paediatrics, Neurology, Surgical

In minor head injury (definition?!), statistically significant correlation between intracranial haemorrhage and:

  • skull fracture
  • focal neurology
  • history of loss of consciousness
  • GCS abnormality (difficult to gauge in preverbal children…)

Headache and vomiting were not found to be predictive and there was great variability in the predictive ability of seizures. (meta-analysis, ArchDisChild 2004;89)

SIGN 110 suggests immediate CT for:

  • GCS less than 14
  • high speed mechanism
  • witnessed loss of consciousness for more than 5 minutes
  • Suspicion of open or depressed skull fracture
  • Any sign of basal skull fracture
  • Tense fontanelle
  • Focal neurological deficit

Otherwise, early (ie within 8 hours) CT should be considered if:

  • bruise/swelling/laceration >5cm on head
  • post-traumatic seizure without epilepsy (and not reflex anoxic)
  • amnesia (antero- or retrograde) >5 minutes
  • suspicion of NAI
  • Significant fall
  • 3+ discrete episodes of vomiting
  • abnormal drowsiness
  • GCS other than 15 in under 1yr old, assessed by experienced provider

If suspicion of NAI, extra rule applies – CT should be done “as soon as child is stable” (and ideally within 24 hrs) if under 1 yr, or neuro signs (incl haemorrhagic retinopathy).

Any loss of consciousness should be assessed, but interestingly retrograde amnesia has to be for >30 minutes to warrant assessment, whereas NICE would do immediate CT! Otherwise 2+ vomits, severe and persistent headache, coagulopathy, difficulties with assessment or social situation, or any other indication for CT.

Admit if any indications for CT, although it also says discharge can be considered if social situation suitable!

NICE head injury (2017) guidelines

similar criteria, but suggests immediate CT for more. Change in practice from admit and watch (Royal College of Surgeons guidelines) to diagnose and decide. Leads to far fewer skull XRs, a lot more CTs and maybe half as many admissions. Some centres have seen cost savings due to earlier discharge.

CT within 1 hour for:

  • age over 1 year, GCS<14 on initial assessment;
  • age under 1 yr; GCS<15 on initial assessment.
  • GCS<15 at 2 hours after injury.
  • age under 1yr plus bruise, swelling or 5cm laceration.
  • Suspicion of NAI.
  • Loss of consciousness >5min (witnessed).
  • Post-traumatic seizure without epilepsy.
  • Abnormal drowsiness.
  • Suspected open or depressed skull fracture, or tense fontanelle.
  • Any sign of basal skull fracture – haemotympanum, panda eyes, CSF leak from ears/nose, Battle’s sign.
  • Focal deficit.

Plus CT within 1 hour if MORE than 1 of the following:

  • Witnessed loss of consciousness more than 5 minutes
  • Abnormal drowsiness
  • 3+ discrete episodes of vomiting
  • Dangerous mechanism eg high speed road traffic accident, fall >3m, high speed projectile
  • Amnesia (retro or antegrade) >5 min

If only 1 of the above, then observe minimum 4 hours – go to CT if during that time:

  • GCS <15
  • Further vomiting
  • Episode of abnormal drowsiness

In children under 10yr, CT for spine should be avoided (risk to thyroid) unless severe head injury (eg GCS<=8), strong suspicion despite plain films, or inadequate plain films. Over 10yr, CT is investigation of choice if:

  • GCS<13 (so 1 point less than for head).
  • intubated.
  • inadequate plain films.
  • Continued suspicion.
  • Needing multi-region scan anyway!

Neuroscience centres are expected to be able to perform initial management of multiple injuries in children. Local guidelines for transfer should be drawn up – there are benefits for being in a neurosurgical centre even if surgery is not required.

Kids with a fracture are not as prone to intracranial lesions as adults, at the same time they are more likely to have intracranial lesion without a fracture!

Note increased risk of malignancy with CT.  So observe for 4 hours if persistent vomiting, review by senior clinician to decide further observation rather than CT. Involve parents in decision [BMJ 2019;365:l1875]

Management

No good RCTs! Avoid secondary brain injury – 1 episode hypotension post head injury triples mortality. Cerebral blood flow is low in first 24hr, peaks at 48hr. Depends on temperature, seizures, pain/anxiety.

Glasgow Coma Score (GCS) 9-12 is moderate, <=8 is severe (equivalent to P or U in AVPU score) and is indication for ventilation to protect airway as reflexes potentially unreliable.

Diffuse axonal injury progresses over 24+ hrs, difficult to see on scan.

Consider external drain/ventriculostomy for intracranial haemorrhage. ?Remove contused brain ?Decompressive craniectomy

Neuroprotective strategy:

  • Head up 30deg, straight
  • Maintain pCO2 at 35-40mmHg
  • Cool if febrile (awaiting data on role of hypothermia). Paralyse to avoid shivering. Paralysis will make seizures difficult to recognise: role for prophylactic anti-epileptics?
  • Analgesia
  • (steroids not helpful)
  • CVP&arterial BP monitoring, ensure adequate perfusion pressure
  • ICP monitoring if neuro signs, GCS <9, post decompression. Bolt gives data but does not allow CSF drainage. ICP takes 7-10 days to settle

For RICP, 3% NaCl 3-5ml/kg bolus – Keep osmo <310mmol/l.

For induction, thiopentone is traditionally used. Ketamine theoretically increases ICP but no real evidence. Adding fentanyl smooths cardiovascular response to procedure.

CT@72h is prognostic.

Shaken Baby: lethargy, vomiting, apnoeas, seizures (40-80%), opisthotonus, irritability. See NAI.

Wilson’s disease

Gastro, General paediatrics, Genetics, Neurology

= hepatolenticular degeneration. Autosomal recessive condition with copper accumulation due to impairment of biliary excretion. Leads to cirrhosis, via a stage indistinguishable from chronic active hepatitis, plus neurological disease. Caused by mutations of the ATP7B gene that codes for a copper transporting ATPase – over 300 mutations known, varying geographically.

Clinical Presentation

Usually presents in late teens but has been described as young as 3yrs. Neurological presentation tends to be older (by 5 years) although they usually have subclinical liver disease. Hepatic disease varies from elevated aminotransferases, through chronic liver disease to fulminant hepatic failure (often with Coombs negative haemolytic anaemia), about 5% of presentations.

Basal ganglia involvement leads to movement disorders viz:

  • Tremor
  • Chorea
  • Parkinsonism
  • Gait disturbances
  • Dysarthria

Other neurological signs are:

  • Psychiatric symptoms
  • Depression
  • Neuroses
  • Personality changes
  • Psychosis

It can also cause:

  • Epilepsy
  • Sunflower cataracts
  • Aminoaciduria
  • Renal stones
  • Osteomalacia with spontaneous fractures

Diagnosis

Can be tricky given multisystem disorder and limited sensitivity/specificity of tests. Heterozygotes may also have borderline results. If typical presentation then diagnosis can be made on basis of:

  • Kayser-Fleischer rings
  • Low serum ceruloplasmin levels (<0.2g/L)
  • Genetic screening of limited utility due to number of known mutations

May require extensive tests of copper metabolism especially with severe hepatic presentation, where up to 50% can have normal ceruloplasmin (an acute phase reactant) eg

  • Non-caeruloplasmin-bound serum copper
  • 24-h urinary copper excretion – can be abnormal in other chronic liver diseases, however. Excretion of >25micromol/24hr after penicillamine is a diagnostic test in children.
  • Liver copper content (>250mcg/g dry weight) – best test when others ambiguous.

In fulminant hepatic failure the following features may suggest diagnosis:

  • Haemolysis (Coombs negative)
  • Alkaline phosphatase surprisingly low viz ALP:Bilirubin ratio of less than 1 has 86% sensitivity and 50% specificity in children

Treatment

  • Diet – chocolate, liver, nuts, mushrooms, and shellfish are high in copper
  • Zinc – reduces copper absorption from gut. Monotherapy is an option for maintenance therapy.
  • Chelation
    • D-penicillamine – but note side effects, and some patients with neurological disease deteriorate on starting treatment
    • Trientine – perhaps less side effects
  • Liver transplantation – curative, except for long-standing neurological disease. Indicated for fulminant hepatic failure.

Monitoring

  • Neurological function
  • Liver function tests
  • 24hr urinary copper excretion (aim for less than 2 micromol/d)
  • Non-ceruloplasmin bound copper of 50-150mcg/L

Tremor

General paediatrics, Neurology

Essential tremor develops insidiously and progresses slowly.  May start in a single limb, but it becomes bilateral over time.  Flexion-extension movement of the wrist, frequency of 4 to 12 Hz. May involve head (yes-yes or no-no). Worsens with stress, fatigue, and may increase with some voluntary activities eg holding a fork or cup. Rest, beta blockers, and alcohol help.  Often a family history.

Compare Cerebellar tremor – low-frequency (less than 5 Hz), intention tremor.  May include postural element (ie at rest).  Other signs include abnormalities of gait and speech, nystagmus, dysdiadochonesis (inability to perform rapid repeated hand movements).  Titubation is the word given to rhythmic movements of head/neck seen in cerebellar disease.

So ask patient to extend arms.  Do Finger-to-nose, finger-to-finger, and heel-to-shin testing (Cerebellar).  Observe drinking from glass, writing name, drawing spiral (or draw within lines of pre-printed spiral).  Check for tone (rigidity), esp when busy using other limb, eg draw a circle in the air) – basal ganglia, eg Parkinsons. Check gait (shuffling?  Ataxic?), eye movements.

Look for signs of space occupying lesion, thyroid or liver disease.  Any chance of intermittent hypoglycaemia?  Panic disorder?  Withdrawal?

Febrile Convulsions

Common, General paediatrics, Neurology

Typical febrile convulsions are:

  • age 6 months to 6 years
  • Normal neurodevelopment
  • generalized, tonic-clonic

Most important differential is CNS infection eg encephalitis, meningitis.  These tend to present with posturing, impaired conscious level, or focal seizures. 15% of patients presenting with status epilepticus with fever have meningitis (observational study) – although low rate of LP so underestimate? I suspect there would have been other features to suggest meningitis beforehand.  Stiff neck? Fear of doing LP due to RICP from fit and/or meningitis, so do CT first if in ICU or abnormal neurology else as soon as no contraindication. If in doubt, treat empirically for meningitis (+/- herpes encephalitis, although risk unknown) with antibiotics and steroids. [Chin RFM, Arch Dis Child 2005;90:66-9.(Ed by Kneen)]

About 30-35% of febrile convulsions in the absence of CNS infection however have one or more complex features:

  • focal onset,
  • duration >10 minutes,
  • or multiple seizures during the illness episode

Febrile status epilepticus, a subgroup of complex febrile convulsions with seizures lasting more than 30 minutes, occur in about 5% of cases.  [BMJ 2015; 351 doi: http://dx.doi.org/10.1136/bmj.h4240 ]

Recurrence

One third of children with febrile convulsions will experience further seizures; age is the single, strongest, and most consistent risk factor. Most recurrences will occur during the first year and over 90% recur within two years (so unlikely to happen later). Other risk factors for recurrence are –

  • family history of febrile convulsions (but not epilepsy) in a first degree relative,
  • children whose initial seizure occurred with a relatively low fever,
  • multiple initial seizures occurring during the same febrile episode.

Surprisingly, status in an otherwise normal child does not appear to significantly increase the risk for further febrile seizures or the development of epilepsy.

Information for Families

From European Journal of Pediatrics 2021:

Viral Meningitis

General paediatrics, Infectious disease, Neurology

Depending on geographic location, different viruses cause viral meningitis.  In some areas, arthropod borne viruses are important.

With new diagnostic methods, more of these cases are being given a specific aetiology.

Complications

Very unusual.  Some small studies have suggested that early enterovirus meningitis linked to later language problems.  Deafness is debatable – some large studies have not found any cases, yet antenatal infections and subclinical viral infections are felt to be causes for deafness in other clinical situations!

Riley Day Familial dysautonomia

Cardiology, General paediatrics, Genetics, Neurology

Seen virtually exclusively in Ashkenazi Jews. Subtype of hereditary
sensory and autonomic neuropathy (cf HSMN).

From birth, absence of tears, poor tone and suck, blotchy skin rashes.
Insensitivity to pain can lead to accidental self mutilation. Speech,
motor development and growth all impaired, but intelligence normal.

Autonomic crises occur, triggered by physical or emotional stress –
sweating, high blood pressure, blotchy rash, vomiting.

Epilepsy

General paediatrics, Neurology

Historically, people with epilepsy were “considered to have unique powers, even hailed as geniuses, regarded as having a sacred disease and leading sacred lives”.&nbsp;&nbsp;But then demonisation, persecution, social rejection. “Epileptic personality” described by psychiatry in 20th century. [Sacred lives, Ian Bone]

Self control is central to our self image and the manner in which we and society believe we should behave. Epilepsy jeopardises this. Patients often conceal. Guilt, loss of confidence and low mood common after seizures.

Definition: At least 2 unprovoked (or reflex) seizures, occurring more than 24hrs apart; else one unprovoked (or reflex) seizure and probability of further seizures similar to that seen in those who have had 2 unprovoked seizures (ie at least 60%); or recognized epilepsy syndrome.  Also part of the definition is that epilepsy is considered “resolved” if age dependent syndrome and past applicable age, or else those who have been seizure free for 10 years and off medication for 5 years. (ILAE 2014)

Note that “seizure” does not have any real medical meaning!  Transient signs/symptoms due to excessive or synchronous neuronal activity in brain (ILAE 2017) – but implies you can tell whether caused by abnormal brain activity, which can be hard!

First assessment:

  • NICE standard is that patient is seen within 2 weeks by a specialist! NICE guideline just says seen by doctor with training and expertise in epilepsy.
  • First assessment should include description of event, age/timing of event, frequency of events.
  • Physical examination of neurology, cardiac, mental state and development.
  • Presence/absence of developmental, learning or schooling problems.

Investigations

EEG

Despite increasing sophistication, interpreting EEG remains an inexact science! Irregular background activity overlaps with detectable abnormality. Plus, only really picks up activity at surface of brain, and can miss simple partial seizures (but not tonic-clonic generalised). Review in 2000 did not find much evidence base. Requires dialogue between referrer and neurophysiologist. Diagnosis remains principally clinical – eg more than 1 tonic-clonic seizure, or multiple absences! Incidence of epileptiform activity in asymptomatic individuals appears to be about 1%, of which a few percent will develop epilepsy over the subsequent years. Abnormal activity is certainly more likely if structural abnormality, but still many will be and remain asymptomatic.<

50% of children with epilepsy have normal EEGs – so not a particularly useful test! Not only that, but in studies, at least 20% of “epileptics” were ultimately given a non-epileptic diagnosis! So request EEG with caution; should be used for confirming clinical opinion, or to guide treatment, not where symptoms are vague. Hence a firm diagnosis of epilepsy and then decisions about treatment may take some time; difficult for families to understand, but it is quite safe to be cautious esp considering the implications of a mistaken diagnosis.

If EEG is negative, then proceed to a sleep EEG (where child is woken by parents at 3am, kept awake then brought to department and allowed to fall asleep during monitoring). This has 80% sensitivity. Failing that, Medilog or Video with continous monitoring. This is good for distinguishing non-epileptic tonic-clonic seizures, but does not rule out co-existing epilepsy.

Good for:

  • status in PICU patients, or non-convulsive status
  • where children too young to describe their symptoms
  • absences – typical absence epilepsy have 3Hz spike and wave with hyperventilation. Highly specific, although absences can be seen in complex partial seizures, which would also be obvious on EEG.
  • indicating underlying brain disease (abnormal background)
  • specific syndromes
  • cognitive impairments that may be seizure related

Beware – an EEG finding of partial epilepsy may not have a surgical lesion! Must be used in conjunction with MRI. A generalized epilepsy may have multiple foci, so if you are unlucky to capture just one you will be misled. Similarly, if secondary generalization occurs rapidly, its partial nature may be missed.

Not usually useful to do after multiple seizures, unless type or frequency changes significantly, in which case a new syndrome/prognosis may have developed.</p>

<p><em>”The brain is subject to maturation; there are multiple protecting and triggering factors, often unpredictable. Seizures may be rare and easy to treat for months and years, but may become more frequent and difficult to control later on. But in many children a precise syndromic diagnosis can be made, and a good final prognosis can be expected in most cases.”</em></p>

Other investigations

All children with recurrent seizures should have an ECG with calculated QTc. &nbsp;Children under 2 with epilepsy or with recurrent focal seizures (other than CECTS) should have an elective MRI brain scan. &nbsp;In most other cases the course is predictable. A normal MRI does not rule out a small dysplastic lesion, equally the finding of a lesion does not mean that it is the cause of the epilepsy. However, at least you can exclude a tumour or malformation.</p>

Focal/partial often have acquired or congenital lesions, often specific precipitating factors eg sleep, startle!</p>

Differential

Management

<p>Consider:</p>

  • Drug treatment (see below) – and risk with prenatal exposure
  • Education – written, peer support
  • Specialist epilepsy nurse review
  • Emergency medication, if appropriate

First aid advice

  • <li><a href=”http://scottishpaeds.org.uk/2017/01/31/living-with-epilepsy/”>Safety advice</a></li>

<li>When/how to access health services</li>

</ul>

</div>

Treatment

Should not be started after first tonic-clonic generalized seizure. Try not to start before EEG done as may mask features.

Refer to tertiary if –

  • child fails to respond to two AEDs appropriate to the epilepsy in adequate dosages over a period of 6 months (SIGN), or 3 over 12 months (NICE)
  • children less than 2 years with epilepsy as defined

SPEN network has pathways for first seizure, new diagnosis, continuing seizures.

See also Living with Epilepsy

VZV encephalitis

General paediatrics, Infectious disease, Neurology

VZV encephalitis presentation not different from usual, viz  fever, headache, altered consciousness, etc. But can be subacute onset.

The more common neuro manifestation of VZV in young children is post-infectious cerebellitis  – usually mild and self limiting, child not unwell but risk of secondary
hydrocephalus in more severe cases.

There is also a well recognized association in childhood  between VZV infection and stroke, usually presents after the rash has cleared – typically 3 months [London study, Miravet & Danchaivijitr 2007).  Post-VZV thromboembolism also seen rarely eg lower limb DVT.

Encephalitis can present early, even before rash (which may
not be very obvious either).  PCR for VZV DNA in the CSF is positive in around a third of patients; VZV specific IgG seen in 90% in CSF. Compare  levels to serum as a way
of confirming CNS involvement.

Usually (not for cerebellitis), steroids given eg 60-80 mg of prednisolone daily for 3 to 5 days) is given (Gilden & Kleinschmidt-DeMasters  2000) esp where MRI evidence of vasculitis.
[encephalitis article, source?]