Neurological problems in advanced cancer - oxford

Question 1

Intracranial hypertension

Answer 1

• tumour, asbcess, hematoma
• disruption of BBB –> increased volume in vault
• slow accumulation has compensation:
  
  • reduced intracranial blood volume
  • increased drainage via circulatory system

Question 2

Clinical features of raised ICP

Answer 2

• altered LOC
• headache
  
  • diffiuse
  • worse supine, cough, valsalva
  • worse in AM
• vomiting
  
  • projectile in posterior fossa lesions
• papilledema
  
  • non sensitive
• focal signs
  
  • CN VI ABDUCENS ***
  • diplopia
• Seizure

Question 3

Acute raised ICP clinical features : Pressure Waves

Answer 3

• Pressure waves
  
  • seconds to minutes
  • agitation, delirium
  • focal or general seizures
  • opisthotonus
  • decerebration
  • amauraosis fugax
  • II, IV, VI palsy (gaze deviation)
  • nystagmus, tinnitus
  • myoclonus
  • dysarthria
  • pyramidal sx
  • hyperthermia, cyanosis, flushing
  • sweating
  • nausea, vomiting, diarrhea, incontinence

Question 4

Brain edema

Answer 4

• loss of osmotically active substances albumin from circulation into brain interstitial tissue
• caused by disruption of BBB by tumour

Vasogenic edema:

• increased extracellular space
• increased capillary permeability
• pathogenesis for tumour induced brain edema

Question 5

Treatment of raised ICP

Answer 5

• goal to maintian CPP and reduce vasogenic edema
• Euvolemia

Positioning - head at 30 degrees

Hypertonic saline

• usually used if refractory to mannitol

Mannitol

• increased blood blow, improved cerebral perfusion
• osmotic gradient between blood and CSF
• diuretic effect

Steroids

• blocks outflow of blood from capillary bed into brain tissue at BBB
• Dexamethasone does not reduce water content in brain tissue
• 48-72 hours to see improvement
• Dex 4-8 mg po q6h
• Children 1 mg / kg initial dose

Question 6

Seizures : definition

Answer 6

• transient occurence of sx due to abnormal excessive neuronal activity in brain
• caused by structural disease (primary and metastatic)
• non structural disease (metabolic and drugs)

Question 7

Seizure classification

Answer 7

• Simple Partial
  
  • normal level of consciousness
  • selective area of cortex involved –> focal symptoms
• Complex partial seizures
  
  • altered LOC with focal symptoms
  • motor automatisms
  • awake, eyes fixed
  • post ictal phase
• Generalized abscence seizures
• Generalized tonic clonic seizures
  
  • sudden LOC
  • muscle rigidity –> cyanosis TONIC
  • myclonus, fasciculations CLONIC
  • post ictal phase

Question 8

AED (Antiepileptic drugs) : Phenobarbital

Answer 8

• partial and tonic clonic
• liver CYP450 metabolism
• slow clearance 4-5 days
• SE:
  
  • drowsiness, ataxia
  • Stevens Johnson syndrome
  • TEN
• 1.5 mg /kg adult
• 3-8 mg/kg children

Question 9

AED : Phenytoin and fosphenytoin

Answer 9

• first line
• simple and complex partial seizures and tonic clonic
• not sedating
• SE:
  
  • ataxia
  • GI
  • hirsutism
  • osteporosis
  • megaloblastic anemia
  • Qtc prolongation
  • hypotension
• drug drug interactions common:
• CYP 450, 3A4 inducer
• significant interaction with DEXAMETHASONE
  
  • can reduce phenytoin plasma levels by 50%
• Contraindications:
  
  • diabetes
  • megaloblastic anemia
  • pancytopenia
  • thrombocytopenia
  • neutropenia

Fosphenytoin

• prodrug of phenytoin
• water soluble
• faster infusion
• IM admin
• lower cardiac related adverse effects
• less local skin irritation

Question 10

AED : Sodium Valproate

Answer 10

• broad spectrum and status epilipticus
• SE :
  
  • tremors
  • sedation
  • ataxia
  • GI sx
  • thrombocytopenia
• sodium channel blockade, GABA, glutamate, NMDA inhibition
• liver toxicity
• hyperammonemia
• metabolism by glucuronidation
• 250-500 mg /day
• children 10-15 mg/kg/day

Question 11

AED : Levetiracetam (Keppra)

Answer 11

• broad spectrum and status
• well tolerated
• SE:
  
  • sedation
  • asthenia
  • dizziness
  • psychosis
• IV/po
• MOA unknown
• does not undergo extensize metabolism
• NO DRUG INTERACTIONS
• metabolites not active
• NO CYP450
• eliminated through kidneys

Question 12

Status epilepticus : definition

Answer 12

• seizure that lasts 30 minutes or more
• two or more seizures without complete recovery inbetween
• likelihood of spontaneous resolution after 5 minutes is small –> treat as status
• Non-convulsive status:
  
  • EEG seizure activity without convulsive activity
  • confusion, psychotic behaviours, automatisms
• Convulsive status epilepticus
  
  • continuous or frequent abnormal motor movements plus altered LOC
  • risk of cerebral damage, acidosis, rhabdo

Question 13

Which AEDs can be given rectally?

Answer 13

• phenobarbital
• carbamazepine
• valproic acid
• lamotrigine
• diazepam

Question 14

Status epilepticus : treatment

Answer 14

• ABC, sugar, labs, reversible causes
• Lorazepam 4-8 mg IV adult, 0.1-0.15 mg/kg children
  
  • half life 10-15 hours
  • onset 3 min
• Midazolam IV or atomized nasal preparation, IM, SC
  
  • water soluble
  • short half life
  • 3 minute onset
• Diazepam IV, rectal (0.2 mg/kg or 10-20 mg)
  
  • PREFERRED RECTAL BENZO
  • high lipid solubility
  • redistributes rapidly to body tissues, and brain concentration falls.
  • needs re-dosing within 20 min
• AED:
  
  • Levatiracetam 20-30 mg/kg IV load over 30 min
  • Phenytoin 20 mg/kg IV load over 60 min

Question 15

Seizure management

Answer 15

• check for reversible causes : hypoglycemia
• ABC
• if self limited, no treatment, but consider AED
• Acute seizure:
  
  • IV lorazapeam first line
  • Clonazepam / midaz subcutaneous
• If no response, see status treatment

Question 16

AED : phenobarbital

Answer 16

• 10-15 mg/kg
• 1-3 mg/kg/day IV or IM, can go in PEG tube
• 60-90 mg sc tid
• for refractory EOL status or recurrent seizures

Question 17

Brain metastases

Answer 17

• lung cancer (multiple lesions)
• breast cancer (1 lesion)
• melanoma
• cause sx by compression, destruction, irritation, edema and bleeding
• Sx:
  
  • headache (night, morning, moderate-severe)
  • nausea/vx
  • decreased LOC
  • Focal signs
  • seizures

Question 18

Treatment of brain metastases

Answer 18

• Surgery if single met with limited or no systemic disease
• WBRT but cog impairment and survival 4-6 months
• stereotactic rt
• Steroids :
  
  • all symptomatic patients with mets or primary brain tumour
  • imrpovement with reduction in peritumoural edema and restoration of BBB
  • Peri-radiation 8-16 mg po od then tapered to lowest effective dose
  • Taper 2-4 mg q5days

Question 19

Leptomeningeal carcinomatosis

Answer 19

• dissemination of cancerous cells through subarachnoid space
• peirpheral circulation, invasion from epidural tumours, perineural invasion, seeding from brain tumour
• multifocal or diffuse
• lung, breast, lymphoma, melanoma
• prognosis 3-6 months

Question 20

Leptomeningeal carcinomatosis symptoms

Answer 20

• variable
• headache
• loc
• radicular pain
• cranial nerves
• polyradiculopathy
• seizure
• multiple symptoms from different levels of neuraxis

Question 21

Diagnosis of leptomeningeal carcinomatosis

Answer 21

• CSF
  
  • malignant cells
  • high opening pressure
  • high protein
  • increased WBC
  • low glucose
• MRI with gadolinium

Question 22

Treatment of leptomeningeal carcinomatosis

Answer 22

• steroids
• radiation sometimes
• systemic chemotherapy
• rarely intrathecal or intraventricular chemo

Question 23

Base of skull lesions: trigeminal nerve

Answer 23

• constant dull well localized pain
• paroxysmal lancinating or throbbing pain
• usually atypical facial pain in distribution of CN V.
  
  • opthalmic branch V1 (5%)
  • maxillary branch V2 common
  • mandibular branch V3 common
• only rarely similar to classic trigeminal neuralgia

Question 24

Numb chin syndrome

Answer 24

• mental nerve involvement
• bony lesions from breast, prostate, advanced head and neck cancers
• disease of the jaw or base of skull
• LMD

Question 25

Glossopharyngeal nerve involvement

Answer 25

• Throat and neck pain
• radiates to ear
• aggravated by swallowing
• local infiltration at neck or base of skull

Question 26

Radiculopathy

Answer 26

• compression of nerve roots by vertebral, paraspinal or LMD
• focal in distribution of nerve
• CT and MRI
• DDX: Herpes zoster and post herpetic neuralgia

Question 27

Cervical plexopathy

Answer 27

• local lancinating pain
• referred to retro auricular and nuchal region
• referred to shoulder and jaw
• sensory abnormalities in nerve root distribution
• DDX:
  
  • post radical neck dissection syndrome
  • post radiation changes
• CT/MRI

Question 28

Brachial plexopathy

Answer 28

• breast, lung, lymphoma
• compression from tumour in axillary, supraclavicular nodes, apex of lung
• neuropathic pain : numbness, dysesthesia, allodynia, hyperasthesia
• Breast and lung : Lower plexus C7-T1
  
  • pain in shoulder, elbow, hand
  • 4th 5th fingers
• costobrachial nerve
  
  • C8-T2
• Upper brachial plexus C5-6
  
  • referred pain to paraspinals, shoulder
  • bicpes, elbow and hand
  • index finger or thumb.

Question 29

Brachial plexopathy : imaging

Answer 29

• CT with contrast
• MRI to look at contiguous epidural space

Question 30

Brachial plexopathy invading epidural space

Answer 30

• Horner’s syndrome
• panplexopathy
• vertebral body erosion
• paraspinal mass on CT

Question 31

Radiation fibrosis vs Brachial plexopathy

Answer 31

Tumour infiltration

• painful 80%
• severe pain
• progressive neurologic dysfunction
• pain progression with dyesthesia
• C7-T1
• can have horner’s sx
• CT : mass with tissue infiltration
• MRI : high signal on T2 weighted images
• EMG : denervation

Radiation fibrosis

• 18% pain
• mild-moderate
• large dose RT
• latency of 6 months- 5years after RT
• progressive weakness
• pain stabilizes once weakness onset
• C5-6
• Absent horner’s sx
• CT: diffuse infiltration of tissue planes
• MRI : low signal intensity on T2
• EMG myokymia

Question 32

Lumbosacral Plexopathy

Answer 32

• colorectal, cervical, bladder, uterine, prostate, sarcoma, lymphoma
• breast, lung, melanoma
• retroperitoneal tumours
• Sx:
  
  • pain in buttocks and legs
  • aching or pressure, rarely burning
  • numbness
  • paresthesia
  • weakness
  • leg edema
• nerve root extension
• muscle extension psoas

Question 33

Pain and paresthesia in inguinal and scrotal region : which nerves?

Answer 33

• L1
• iliohypogastric nerve
• ilioinguinal nerve
• genitofemoral nerve in

Question 34

Sacral plexopathy

Answer 34

• presacral mass invading sacrum
• rectosigmoid and bladder carcinomas
• hydroureter hydronephrosis
• coccygeal plexus:
  
  • sphincter dysfunction
  • saddle sensory loss

Question 35

Mononeuroapthy

Answer 35

• less common
• compression infiltration of nerve by bony lesion or soft tissue mass in limbs
• intercostal nerve neuropathy
• obturator, femoral, sciatic nerve
• peroneal mononeurpathy head of fibula or popliteal fossa

Question 36

Peripheral nerve compression treatment

Answer 36

• opioids
• adjuvants
• dexamethasone

Question 37

Clinical findings in lumbar plexopathy due to cancer

Answer 37

• L2-L4
  
  • lower abdomen
  • flank, iliac crest
  • anterolateral thigh
  • Motor :
    
    • proximal leg weakness
    • hip flexors
    • patellar reflex
    • no anal sphincter weakness
• L5-S1
  
  • buttock, perineal pain
  • posterolateral thigh, leg radicular pain
  • paresthesias to perineum, thigh, sole
  • Motor
    
    • distal leg weakness
    • ankle reflex
  • tenderness to sacrum
• Panplexopathy
  
  • variable
  • L2-S2

Question 38

Peripheral neuropathy

Answer 38

• stocking glove
• loss of sensation
• burning dysesthesia, allodynia, hyperalgesia
• early sign reduction or loss of ankle reflex
• muscle cramps

Question 39

Cisplatin CIN

Answer 39

• sensory neuropathy
• cells of dorsal root ganglia
• primary involvement of large fibre functions of proprioception
• ataxia
• less painful

Question 40

Vincristine and paclitaxel

Answer 40

• early sensory loss, later weakness
• pain
• sensory axonopathy with some motor component

Question 41

Polyneuropathy and peripheral neuropathy : related to cancers

Answer 41

• myeloma
• paraneoplastic
• nutritional factors (cachexia, b12, folate)
• hepatic, renal dysfunction
• infiltration of peripheral nerves (lymphoma, leukemia)
• vascular peripheral nerve lesions

Question 42

Polyneuropathy and peripheral neuropathy : related to chemotherapy and radiation

Answer 42

• vincristine
• cisplatin
• platins
• paclitaxel
• thalidomide
• radiation of limbs

Question 43

Paraneoplastic syndromes

Answer 43

• immune mediated mechanism
• antibodies

Question 44

Lambert Eaton myasthenic syndromes (LEMS)

Answer 44

• 3% SCLC patients
• antibodies against presynaptic membrane
• impaired acetylcholine release
• muscle weakness, fatigue, pain
• legs
• proximal muscles weakness
• improves with use (warm up syndrome)
• worse in high temperature
• absent reflexes
• autonomic changes

EMG, antibody testing

Treatment : immunosuppression, plasmapheresis

Question 45

Myasthenia Gravis

Answer 45

• associated with THYMOMA (15%)
• antibodies against aceytlcholine receptors

Presentation

• fatiguable weakness without sensory or coordination problems
• worse with use
• better with rest or cold temperatures
• diplopia
• pstosis
• dysphagia to solids
• slurred speech

Dx:

• tensilon test
• give acetylcholinesterase inhibitor and check for reveral of grip strength weakness in 30 seconds

Treatment

• acytelcholinesterases (meostigmine)
• steroids
• thymectomy