CNS Disease 2dry to Infection

Question 1

Acute Disseminated Encephalomyelitis (ADEM)

Answer 1

Acute disseminated encephalomyelitis (ADEM) is an autoimmune demylinating disease of the central nervous system. It may also be termed post infectious encephalomyelitis. The aetiology is not fully understood and it can occur following infection with a bacterial or viral pathogen. Common infections include measles, mumps, rubella, varicella and small pox, however this list is not exhaustive.

After a lag time of between a few days to 2 months there is an acute onset of multifocal neurological symptoms with rapid deterioration. Non-specific signs such as headache, fever, nausea and vomiting may also accompany the onset of illness. Motor and sensory deficits are frequent and there may also be brainstem involvement including occulomotor defects.

There are no specific biomarkers for the diagnosis of ADEM. MRI imaging may show areas of supra and infra-tentorial demylination. Management involves intravenous glucocorticoids and the consideration of IVIG where this fails.

Question 2

ADEM - Example Question

Answer 2

A 26-year-old female from the travelling community presents to A&E following a seizure. History from her family suggests that she was suffering with headaches over the last 24 hours and this morning was feverish and vomiting. Her partner says she was unwell 1 month ago with a fever and whole body rash that spontaneously resolved. There is no other significant past medical history.

On examination she appears drowsy. She has a left sided hemiparesis with bilateral nystagmus. Fundoscopy reveals papiloedema. There are no skin rashes.

What is the most likely underlying diagnosis?

Meningococcal septicaemia
Meningitis secondary to herpes simplex virus
Progressive multifocal leukoencephalopathy (PML)
Multiple sclerosis
Acute disseminated encephalomyelitis (ADEM)

In the case given there is no history of preceding neurological symptoms and the acute onset of the neurology points away from the diagnosis of MS. In the examination findings it is specified there is no rash making meningococcal septicaemia very unlikely. PML is only seen with significant immunosupression and presents with a subacute picture. This leaves HSV as a plausible diagnosis however ADEM secondary to measles is more likely given the previous full body rash in a member of the travelling community who may not have been vaccinated.

Question 3

Intracerebral Abscess

Answer 3

Intracerebral abscess

Features
fever
headache
seizures
signs of raised intracranial pressure
focal neurological deficits

Management
surgical drainage: supratentorial abscesses may be drained via a burr hole
antibiotic therapy

Question 4

BACTERIAL MENINGITIS - CSF

Answer 4

Appearance = Cloudy

Glucose = Low (<1/2 of plasma)

Protein = High (> 1 g/l)

WCC = 10 - 5,000 polymorphs/mm³

Question 5

VIRAL MENINGITIS - CSF

Answer 5

Appearance = Clear/Cloudy

Glucose = 60-80% of plasma glucose*
*mumps is unusual in being associated with a low glucose level in a proportion of cases. A low glucose may also be seen in herpes encephalitis

Protein = Normal/Raised

WCC = 15 - 1,000 lymphocytes/mm³

Question 6

TB MENINGITIS - CSF

Answer 6

Appearance = Slightly cloudy/Fibrin Web/Turbid

Glucose = Low (<1/2 of plasma)

Protein = High (> 1 g/l)

WCC = 10 - 1,000 lymphocytes/mm³

NB: The Ziehl-Neelsen stain is only 20% sensitive in the detection of tuberculous meningitis and therefore PCR is sometimes used (sensitivity = 75%)

Question 7

TB MENINGITIS - Example Question:

Answer 7

A 23 year-old artist presents after he woke up with headache, neck stiffness, and photophobia. He is normally fit and well, but for the last three weeks has complained of feeling tired and irritable.

On examination, the left side of the palate does not elevate, and the tongue is deviated to the left upon protrusion. The remainder of the neurological examination is unremarkable.

Plain computed tomography of the head is unremarkable.

Lumbar puncture is performed with results of CSF analysis as follows:

Appearance	Turbid
White blood cells	28 cells/mm³ (95% lymphocytes)
Red blood cells	<1 cells/mm³
Gram stain	No organisms seen
Protein	1.32 g/L
Glucose	1.4 mmol/L
Serum glucose	7.5 mmol/L

What is the most likely diagnosis?

	Meningococcal meningitis
	> Tuberculous meningitis
	Subarachnoid haemorrhage
	Skull base tumour
	Malignant meningitis

The prodromal phase of malaise and possible personality change, followed by meningism, with the onset of basal cranial nerve palsies, and coupled with the CSF findings of lymphocytic pleocytosis, raised protein, and low glucose, are all highly suggestive of tuberculous meningitis.

There is no particular suggestion of a primary malignancy, but malignant meningitis (leptomeningeal carcinomatosis) is a possibility and it would be reasonable to send a large volume of CSF for cytology. Like tuberculous meningitis, this condition typically presents with headache, meningism, and cranial nerve palsies. However, it is eye movements which are most often affected. There is often also invasion of spinal meninges which involves nerve roots and mimics radiculopathy. The CSF is hardly ever normal, although there are no specific features other than the direct demonstration of malignant cells.

Meningococcal meningitis is an acute disease, so the three week prodrome described here would be unusual. The presence of cranial nerve palsies would be extremely unusual. The CSF would be expected to show a neutrophilic pleocytosis, with a low glucose (less that 50% of serum glucose), but not as low as in tuberculous meningitis.

Subarachnoid haemorrhage should be considered in any case of acute headache. The normal CT scan is reassuring but does not exclude the diagnosis, but in any case the CSF is not suggestive.

A tumour of the skull base might explain the lower cranial nerve palsies, but one would have expected some more suggestive symptoms and an abnormal CT head. This diagnosis would not explain the grossly abnormal CSF findings.

Question 8

Malignant Meningitis

Answer 8

If there is a suggestion of primary malignancy, consider malignant meningitis (leptomeningeal carcinomatosis).

In this situation, it would be reasonable to send a large volume of CSF for cytology. Like tuberculous meningitis, this condition typically presents with headache, meningism, and cranial nerve palsies.

However, it is EYE MOVEMENTS which are most often affected.

There is often also invasion of spinal meninges which involves nerve roots and mimics radiculopathy.

The CSF is hardly ever normal, although there are no specific features other than the direct demonstration of malignant cells.

Question 9

NORMAL CSF RESULTS

Answer 9

Normal lumbar puncture results:
Appearance: Clear
Opening pressure: 10-20 cm H2O
WBC count: 0-5 cells/µL
Glucose level: >60% of serum glucose
Protein level: < 45 mg/dL

Question 10

Guillian-Barre CSF Results

Answer 10

Guillain Barré syndrome causes a clear CSF sample, a normal or elevated opening pressure, a normal or elevated white cell count, a normal glucose with an elevated protein level.

Question 11

HSV Encephalitis CSF Results

Answer 11

Features of cerebrospinal fluid analysis in HSV encephalitis include an elevated white blood cell count with lymphocytic predominance and an elevated protein.

Question 12

TB Meningitis CSF Results

Answer 12

Tuberculosis causes a clear or opaque CSF sample, an elevated opening pressure, a raised white cell count, a very low glucose and an elevated protein

Question 13

Bacterial Meningitis CSF Results

Answer 13

Bacterial meningitis causes a clear, cloudy or purulent CSF sample, an elevated opening pressure, raised white cell count (unless partially treated), low glucose (<40% of serum glucose) and an elevated protein count.

Question 14

Herpes Simplex Encephalitis

Answer 14

Herpes simplex (HSV) encephalitis is a common topic in the exam. The virus characteristically affects the temporal lobes - questions may give the result of imaging or describe temporal lobe signs e.g. aphasia

Question 15

HSV Encephalitis - Features

Answer 15

Features
fever, headache, psychiatric symptoms, seizures, vomiting
focal features e.g. aphasia
peripheral lesions (e.g. cold sores) have no relation to presence of HSV encephalitis

Pathophysiology
HSV-1 responsible for 95% of cases in adults
typically affects temporal and inferior frontal lobes

Investigation
CSF: lymphocytosis, elevated protein
PCR for HSV
CT: medial temporal and inferior frontal changes (e.g. petechial haemorrhages) - normal in one-third of patients
MRI is better
EEG pattern: lateralised periodic discharges at 2 Hz

Mx = IV ACICLOVIR

The prognosis is dependent on whether aciclovir is commenced early. If treatment is started promptly the mortality is 10-20%. Left untreated the mortality approaches 80%

Question 16

CSF Results - Diagnosis! Example Question

Answer 16

A 64 year-old man presents to the Emergency Department with his family. His wife is concerned about his behaviour during the past week. He has been intermittently confused, and sleeping during the day. Both of which is abnormal for him.

On examination, he is alert and looks well. He has mild neck stiffness, with no photophobia. The rest of the neurological examination is normal.

A CT scan reveals no abnormality.

An electroencephalography shows generalised slowing.

Hb 130 g/l
Platelets 232 * 109/l
WBC 14 * 109/l
Serum glucose 9 mmol/L

Which lumbar puncture result would most likely support your diagnosis?

Opening pressure: 14 cm H20
WCC- 2 cells/µL
Glucose- 7
Protein- 30 mg/dL

Opening pressure: 28 cm H2O
WCC- 500 cells/µL (>90% polymorphonucleocytes)
Glucose- 3.5
Protein- 65 mg/dL

Opening pressure: 18 cm H2O
WCC- 5 cells/µL
Glucose- 8
Protein- 65 mg/d

> Opening pressure: 22 cm H2O
WCC- 100 cells/µL (lymphocytic predominance)
Glucose- 8
Protein- 54 mg/d

Opening pressure: 33 cm H2O
WCC- 450 cells/µL
Glucose- 2
Protein- 65 mg/d

This patient likely has encephalitis. The most likely causative organism is herpes simplex virus.

Features of cerebrospinal fluid analysis in HSV encephalitis include an elevated white blood cell count with lymphocytic predominance and an elevated protein.

Normal lumbar puncture results:
Appearance: Clear
Opening pressure: 10-20 cm H2O
WBC count: 0-5 cells/µL
Glucose level: >60% of serum glucose
Protein level: < 45 mg/dL

Bacterial meningitis causes a clear, cloudy or purulent CSF sample, an elevated opening pressure, raised white cell count (unless partially treated), low glucose (<40% of serum glucose) and an elevated protein count. (answer 2)

Guillain Barré syndrome causes a clear CSF sample, a normal or elevated opening pressure, a normal or elevated white cell count, a normal glucose with an elevated protein level. (answer 3)

Tuberculosis causes a clear or opaque CSF sample, an elevated opening pressure, a raised white cell count, a very low glucose and an elevated protein. (answer 5)

Question 17

Progressive multifocal leukoencephalopathy (PML)

Answer 17

This is a demyelinating disease of the CNS characterised by widespread lesions due to brain infection of oligodendrocytes by the JC Virus (JCV). These are visible on an MRI and have a characteristic appearance. The signs correspond to the areas occupied by the lesions. PML occurs almost exclusively in immunocompromised patients such as those with HIV or on immunotherapy. You should consider PML in your differential in such patients when they present with new odd neurology and an abnormal MRI scan.

Question 18

PML Diagnosis - Example Question

Answer 18

A 36-year-old lady on natalizumab for relapsing-remitting multiple sclerosis develops left leg weakness. Over 3 weeks this progresses to left hemiparesis and visual impairment. She also notices poor memory and struggles to process numbers at work as an accountant. Examination reveals left-sided 4/5 power, right homonymous hemianopia, and an abbreviated mini-mental state score of 21/30. Routine blood tests are unremarkable. MRI brain shows new multiple confluent lesions in the parietooccipital and right motor white matter areas as well as the left occipital area, with no mass effect or enhancement. Which of the following tests is likely to be most helpful in establishing a diagnosis?

	Serum glucose
	HIV serology
	> JC Virus serology
	Cerebral angiogram
	Full blood count (FBC)

The diagnosis here is progressive multifocal leukoencephalopathy (PML). This is a demyelinating disease of the CNS characterised by widespread lesions due to brain infection of oligodendrocytes by the JC Virus (JCV). These are visible on an MRI and have a characteristic appearance. The signs correspond to the areas occupied by the lesions. PML occurs almost exclusively in immunocompromised patients such as those with HIV or on immunotherapy. You should consider PML in your differential in such patients when they present with new odd neurology and an abnormal MRI scan.

This question’s other aim is to introduce to you one of the newer therapies in multiple sclerosis (MS) called nataluzumab. It is actually very frequently used in MS and indeed now approved for the treatment of relapsing-remitting MS (RRMS) in more than 50 countries. It is a monoclonal antibody that inhibits the migration of leucocytes into the central nervous system, hence reducing inflammation and demyelination. It is given as an IV infusion once a month. It is indicated in patients getting relapses despite treatment with interferon-beta or patients who just have rapidly evolving severe RRMS. It has been shown to decrease the risk of progression of disability by 42-54% and the annualised rate of relapse by 68%. The two principle side-effects are hepatotoxicity and increased PML risk, and we monitor patients for these with monthly liver function tests (LFTs) and 6-monthly JCV serology. It would not be unreasonable of them to expect you to know something about nataluzumab in the exam (especially to recognise PML as a side-effect) given that the drug is now in such common use.

Question 19

BOTULISM

Answer 19

Botulism

Clostridium botulinum
gram positive anaerobic bacillus
7 serotypes A-G
produces botulinum toxin, a neurotoxin which irreversibly blocks the release of acetylcholine
may result from eating contaminated food (e.g. tinned)
neurotoxin often affects bulbar muscles and autonomic nervous system

Features
patient usually fully conscious with no sensory disturbance
flaccid paralysis
diplopia
ataxia
bulbar palsy

Treatment with antitoxin is only effective if given early - once toxin has bound its actions cannot be reversed

Therapeutic uses of botulinum toxin
strabismus
dystonias: torticollis, blepharospasm
hyperhidrosis
cosmetic: Botox: serotype A of botulinum toxin used

Question 20

BOTULISM - Example Question

Answer 20

A 23 year old white Caucasian left-handed male presents with a 24 hour history of slurred speech. He is a ‘frequent flyer’ in the Emergency Department with repeated admissions and known is a known user of intravenous drugs and alcohol. His past medical history includes depression and previously treated in adolescence for functional neurological symptoms. He denies having had a drink for the past 2 weeks but used intravenous cocaine yesterday.

On examination, he is obviously unkempt and a lack of prominent veins. There is an old abscess scar over his right femoral crease. His speech is markedly slurred but he remains orientated to time and place. You also note significant loss of forehead creasing and facial weakness on both sides of his face with normal facial sensation. In addition, his power his 4-/5 in shoulder abduction, shoulder adduction, hip flexion and hip extension, with 5/5 power on all other movements. Reflexes were present in biceps, supinator, patella and ankle, with absent triceps reflex. Both plantar reflexes were downgoing. Sensation to cotton wool, proprioception and pin prick was normal, with the patient reporting no pain.

What is the diagnosis?

	Heavy metal intoxication
	Guillain Barre syndrome
	> Botulism
	Chronic inflammatory demyelinating polyneuropathy (CIDP)
	Myasthenia gravis

The patient has presented with bilateral cranial neuropathies and symmetrical proximal weakness, in the context of intravenous drug use. The descending pattern of weakness, is atypical for Guillain Barre syndrome. The time course of within 8 weeks also rules out CIDP. Myasthenia gravis is a possibility but there is no suggestion of fatiguability. The distinction between heavy metal intoxication and botulism is difficult: intravenous drug users, particularly those sourcing from Eastern Europe, who have been known to present with manganese poisoning due to dirty constituents. Clinical features of course depend on the precise metal involved but acute poisoning typically include encephalopathy, gastrointestinal upset and myalgia in addition to peripheral neuropathy. Significant sensory neuropathy causing neuropathic pain is commonly prominent. In the case of this patient, with bilateral cranial neuropathies and symmetrical proximal weakness, in the context of intravenous drug use, makes botulism most likely. Treatment is with antitoxin, removal of the original source of infection in addition to close monitoring of respiratory function.

Question 21

Ramsay Hunt Syndrome

Answer 21

= Herpes Zoster Oticus
Caused by reactivation of varicella zoster virus in the GENICULATE ganglion of the 7th cranial nerve

Features:

• Auricular pain often 1st feature
• Facial nerve palsy
• Vesicular rash around ear
• Other features include Vertigo, Tinnitus

Vesicular lesions are more classically seen in external auditory canal and pinna, they may also be seen on the anterior 2/3 of the tongue and soft palate

Mx = Oral Aciclovir and Corticosteroids usually given

Question 22

Herpes Zoster Opthalmicus

Answer 22

Reactivation of varicella zoster virus in area supplied by ophthalmic division of trigeminal nerve = 10% of shingles cases

Features:

• Vesicular rash (erythematous, blistering) which may or may not involve the actual eye itself
• PAIN (Burning)
• HUTCHINSON’S SIGN = Rash on tip or side of nose indicates nasociliary involvement and is strong RF for ocular involvement

Cx:

• Ocular - Conjunctivitis, Keratitis, Episcleritis, Anterior uveitis
• Ptosis
• Post-herpetic neuralgia

Mx:
- Oral antiviral treatment for 7-10d, ideally started within 72h
NB Topical antiviral treatment not given in HZO
- Oral corticosteroids may reduce duration of pain but do not decrease incidence of post hepatic neuralgia
- IF OCULAR INVOLVEMENT > URGENT OPHTHALMOLOGY REVIEW

Question 23

Intracerebral Abscess - Example Question

Answer 23

A 35-year-old man is brought into the Emergency Department after 3 successive tonic-clonic seizures. He was given 10mg of rectal diazepam and has since stabilised.

A brief history from his girlfriend states that he was usually fit and well apparent from recurrent sinusitis. Over the past month, however, he had been complaining of increasing headaches and had received a course of antibiotics from his GP.

He takes no regular medication but his partner states that they do occasionally take ecstasy whilst on nights out.

On examination, he is drowsy with a Glasgow Coma Scale (GCS) of 12. His temperature is 38.8 degrees Celsius, his pulse is 57 bpm and regular, blood pressure 150/90 mmHg, oxygen saturations 97% on 15L oxygen via a non-rebreathe mask.

Cardiovascular examination reveals normal heart sounds, capillary refill time of 3 seconds. His calves were soft and non-tender. His chest was clear with no signs of consolidation. Abdominal examination was unremarkable.

Neurological examination was difficult in view of the patients low GCS but no focal abnormality could be detected. On attempt to passively flex his neck he became agitated and obviously uncomfortable. Pupils were equal and reactive to light. Fundoscopy demonstrated bilateral oedematous optic discs.

Bloods were as follows:

Na+	130 mmol/L
K+	3.9 mmol/L
Urea	5 mmol/L
Creatinine	80 µmol/L
Hb	160 g/L
WBC	25.0x10^9/L
Neutrophils	91%
LFTs	Normal
CRP	90 mg/L

Based on the findings above, what is the most likely diagnosis?

	> Intracerebral abscess
	Sepsis secondary to sinusitis
	Ecstasy overdose
	Meningitis
	Cerebral lymphoma

This is a 30-year-old man who presented with a history of headaches, seizures and a fever. The history of headaches and a course of antibiotics could suggest partially treated sinusitis. This has likely extended posteriorly resulting in an intracranial abscess as indicated by the inflammatory markers, signs of raised intracranial pressure and seizures.

Meningitis can sometimes present with seizures if this has progressed to meningoencephalitis but the history of recurrent sinusitis and headaches with raised intracranial pressure are more suggestive of a space occupying abscess.

Although ecstasy overdose can cause pyrexia and seizures, it is not in keeping with the chronic progression of this patient’s symptoms.

Seizures have been associated with severe sepsis but it is not in keeping with all of the signs and symptoms demonstrated here.

Question 24

HSV Encephalitis - Example Question

Answer 24

A 46-year-old Ghanaian woman was flying from Ghana to San Francisco, USA when she was noticed to be confused and behaving inappropriately on the plane. She was talking loudly to herself, complaining of a headache, and also appeared to be hearing voices. She had one episode of incontinence on the plane. During the transit in London, she was brought to the nearest hospital for investigations.

On examination, she was drowsy and slow to respond to questions. Her temperature was 37.3ºC, heart rate of 98 bpm, blood pressure of 138/92 mmHg, respiratory rate of 16, and oxygen saturations were 100% on air. Her pupils were 3mm bilaterally, equal and reactive. Her neck was supple and there was mild photophobia. Her abbreviated mental test score was 6/10.

Her investigations revealed:

C Reactive protein	24 mg/l
Haemoglobin	128 g/l
White cell count	11.6 x 10^9/L
HIV antibody serology	positive
HIV viral load	19000 copies/ml
CD4+ T lymphocyte count	35 cells/mm³
Na+	136 mmol/l
K+	4.9 mmol/l
Urea	7.2 mmol/l
Creatinine	108 µmol/l
Corrected calcium	2.32 mmol/l
Plasma glucose	5.8mmol/l

Chest X-Ray: Lung fields clear
Computer Tomography (CT) head scan: Hypodense lesions involving the medial temporal regions. Lesions enhance with contrast.

Cerebro-spinal fluid (CSF) analysis:

Opening pressure	20 cmH2O
Protein	1.2 g/L
White cell count	50 per mm³ (predominantly mononuclear cells)
Red cell count	5 per mm³
Glucose	4.8 mmol/l
Gram stain	No organisms seen

What is the next most appropriate management step?

	> Intravenous acyclovir
	Oral prednisolone
	Highly Active Anti-Retroviral Therapy (HAART)
	Intravenous fluconazole
	Pyrimethamine and Sulfadiazine

This lady is immunocompromised with a new diagnosis of HIV, and has an altered conscious level, with psychotic symptoms suggestive of encephalitis. Her CT head scan shows the involvement of the medial temporal region, which is highly suggestive of herpes encephalitis, and this is supported by the LP results with raised protein levels, and a predominantly mononuclear white cell picture. Viral polymerase chain reaction (PCR) is the gold standard in the diagnosis of herpes encephalitis, and management for Herpes encephalitis is high-dose intravenous acyclovir to achieve central nervous system penetrance.

Although this lady has advanced HIV infection, there is some evidence that starting HAART may cause an immune reconstitution syndrome, resulting in an initial deterioration in the patient’s condition as the immune system is boosted. Thus while she would require HAART, the initial management should be to decrease the burden of infection with acyclovir to prevent a deterioration in her condition.

There is limited evidence for steroid use in HSV encephalitis. There is no evidence of cryptococcal or toxoplasmosis infection from the CT and CSF results, which rules out options (d) and (e) respectively.

Question 25

CSF - Putting it all together

Answer 25

NORMAL CSF
Appearance= Clear
Opening Pressure: 10-20cm H2O
Glucose: >60% plasma glucose
Protein: < 45mg/dL
WCC: 5-10/mm3 = 0-5/microlitre

BACTERIAL MENINGITIS CSF
Appearance = Cloudy
Opening Pressure = Elevated opening pressure
Glucose: Low <50% plasma glucose 
Protein: Elevated >1g/L (50-100mg/dL) 
WCC:  Elevated 
10 - 5,000 polymorphs/mm³ = 100-5000 cells/mL
Polymorphonuclear Leukocytes predominate

VIRAL MENINGITIS CSF
Appearance = Clear
Opening Pressure = Normal
Glucose: High 60-80% of plasma glucose (except mumps and possibly HCV encephalitis = low)
Protein: Normal/Raised
WCC: Elevated 
15 - 1,000 lymphocytes/mm³ = 10-500 cells/mL
Lymphocytes predominate

TB MENINGITIS CSF
Appearance = Turbid/Fibrin web
Opening Pressure = Elevated
Glucose: V Low - <50% plasma glucose 
Protein: Elevated >1g/L (50-100mg/dL)
WCC: Elevated
10 - 1,000 lymphocytes/mm³ = 0-1000 cells/mL
Lymphocytes predominate

FUNGAL MENINGITIS CSF
Appearance = Fibrin web
Opening pressure = Elevated (Cryptococcus >25cm H20)
Glucose: Normal to decreased
Protein: Elevated
WCC: Normal to elevated
0-500 cells/mL Lymphocyte predominant

Features of cerebrospinal fluid analysis in HSV encephalitis include an elevated white blood cell count with lymphocytic predominance and an elevated protein.

Guillain Barré syndrome causes a clear CSF sample, a normal or elevated opening pressure, a normal or elevated white cell count, a normal glucose with an elevated protein level.

Question 26

Differentiating between Botulism and Heavy metal poisoning

Answer 26

The distinction between heavy metal intoxication and botulism is difficult: intravenous drug users, particularly those sourcing from Eastern Europe, who have been known to present with manganese poisoning due to dirty constituents.

Clinical features of course depend on the precise metal involved but acute poisoning typically include encephalopathy, gastrointestinal upset and myalgia in addition to peripheral neuropathy. Significant sensory neuropathy causing neuropathic pain is commonly prominent.

Botulism e.g. bilateral cranial neuropathies and symmetrical proximal weakness, in the context of intravenous drug use. No sensory involvement. Treatment is with antitoxin, removal of the original source of infection in addition to close monitoring of respiratory function.