Neurological symptoms
In the palliative care setting, neurologic symptoms may be
caused by a variety of factors including primary and metastatic
malignancies, neurodegenerative disease and the side effects of
medications. Treatment should take into account the underlying
disorder and the site of any lesion or lesions. In many cases there
may not be a definitive treatment available although symptoms can
usually be controlled.
Cancer involving the central nervous system is the second most
common paediatric malignancy with the most common tumours being
astrocytomas and medulloblastomas. Central nervous system tumours
can also arise as metastases of other malignancies such as
lymphoma. Neurological symptoms will vary with the type and
location of the tumour.
Individually, neurodegenerative diseases are rare but as a group
they account for a large proportion of children who require
palliative care. The aetiology of neurodegenerative disorders is
varied but metabolic and other genetic abnormalities are major
causes. For some children a specific cause can not be identified.
Children with neurodegenerative conditions tend to have protracted
courses. They are often well at the time of diagnosis with the slow
and insidious onset of symptoms. Their clinical condition then
deteriorates inexorably and many children spend long periods in
states of high dependency.
Myoclonus
Myoclonus, the brief and irregular contraction of all or part of
a muscle, can occur as a result of immobility, pain, or other
sensory stimulation. It is also a recognised side effect of opioid
use, particularly pethidine ®1 and is more common where the patient
has renal impairment. It is postulated that the major cause is
accumulation of opioid metabolites, but the dose at which it occurs
varies widely.
Treatment of myoclonus may not be necessary if it is not
troubling the patient. If required it may be appropriate to reduce
the dose of opioid, change the route of administration or change to
another drug. Benzodiazepines are useful in the management of
myoclonus with alternatives including
- Oral diazepam 0.05-0.1mg/kg q4-6h (max 5mg/dose)®2
- Oral or sublingual clonazepam (0.01mg/kg q8-12h) ®2
- Midazolam as a continuous S/c or IV infusion ( see seizure
management) is usually effective. 8-30micrograms/kg/hr®2
Muscle Spasm
Muscle spasm, the involuntary and painful contraction of
skeletal muscle (usually flexor), generally occurs in the context
of upper motor neuron lesions and has the potential to cause
significant discomfort. The problem may be exacerbated by pain,
constipation or other factors. Therapeutic options include
- Baclofen 0.5mg/kg/day orally in 3-4 doses
increasing gradually at 3 day intervals to 2mg/kg/day in 3-4
doses.®3. Baclofen may also be effective intrathecally.
- Dantrolene
- Diazepam IV 0.1-0.3mg/kg/dose repeated 1-4
hrly as required up to max of 0.6mg/kg within 8 hours
Or
Oral 0.05-0.3mg/kg/dose q8-12h ®3
Seizure
Management in Children over six months of age
Children with primary or metastatic tumours of the brain,
metabolic disturbances or genetic disorders may be at increased
risk of seizures. It can be distressing for family members to
witness a seizure and parents may find it helpful to have general
information, as well as a plan of action, should a seizure occur.
Treatment can be separated into two components: emergency
management and prophylactic treatment.
Emergency management of
Seizures
It is extremely helpful to have a supply of anticonvulsant
medication in the home for emergency use by the family or support
services if the child has a seizure. Diazepam 0.3-0.5mg
rectally ®3 is effective. Rectal administration is a
technique easily learnt by families and kits are available through
the pharmacy at the RCH. Diazepam should not be given rectally in
children at risk of neutropenia.
Diazepam should NOT be given
intramuscularly or subcutaneously as it is irritant to
tissue.
In circumstances where rectal administration is difficult or
undesirable, clonazepam 0.01 mg/kg can be used
orally. ®2 Clonazepam is available in an oral drop preparation such
that extremely small volumes can be given even if the child is
having a seizure. Sublingual absorption is rapid and the dose can
be repeated.
Midazolam is an alternative anticonvulsant. The parenteral
preparation can be administered directly onto the buccal
mucosa or intranasally in a dose of
0.3-0.5mg/kg/dose (max 10mg). ®4
If the child is unable to tolerate either oral or rectal
administration of anticonvulsants, midazolam can
be given either IV or SC. For emergency seizure management the dose
is
Midazolam 0.15 mg/kg IV or SC stat then 2 micrograms/kg/min
increasing by 2 micrograms/kg/min until seizures cease (max 24
micrograms/kg/min)®3
Maintenance treatment
of seizures
Medications used for emergency management of seizures do not
have a prolonged effect, and if fitting is likely to be an ongoing
problem, maintenance treatment is indicated. In the palliative care
setting phenytoin, phenobarbitone and carbamazepine may be helpful
and can be given orally. For patients who cannot tolerate or absorb
oral medications midazolam can be administered. Midazolam has the
advantage of being compatible with morphine and they can be
combined in the same syringe driver thus making delivery
simpler.
- Phenobarbitone and clonazepam can also be administered
subcutaneously and are effective alternatives.
Seizure management in neonates and infants under six months of
age
Seizure management in neonates deserves special mention. As with
older children, the oral, oro-gastric or naso-gastric route is
preferred for administration of medications. However, due to
differing pharmacokinetics, drugs and dosages differ from those
used in older children. Phenobarbitone is the drug of choice in
controlling neonatal seizures. The table below shows drugs in order
of preference, loading doses if appropriate and maintenance doses.®
3
| Drug | Loading dose | Maintenance dose |
| Phenobarbitone | 20mg/kg I.V(Dose may be divided into half) | 3-5 mg/kg/Day I.V/Oral |
| Phenytoin | 20 mg/kg I.V | 4 mg/kg/day I.V/Oral |
| Clonazepam | <0.25 mg I.V(prem or not on ventilator infants 0.1-0.2 mg
I.V) | 0.01-0.03 mg/kg/day Oral |
If the infant becomes drowsy or is unrousable anticonvulsants
should be ceased, if subsequent fitting occurs then these should be
managed using clonazepam. In infants who are offered comfort
feeding only, seizures are rarely a problem. It is important to
understand that the management of neonatal patients in the
community setting is complex and should be undertaken with the
support of a neonatal unit and skilled neonatal paediatricians.
Restlessness,
Agitation and Delirium
Restlessness and agitation are not uncommon in the terminal
phase of illness and while there may be no apparent cause,
uncontrolled pain, hypoxia, anxiety and medications can contribute
to the development of these symptoms. Management centres around
treatment of the underlying cause (if appropriate), nursing the
child in a quiet and safe environment and using medications where
necessary. Families may need reassurance that restlessness and
agitation are often a part of the dying process and also need to
understand that while difficult to witness, it may not be troubling
the child. Support in the home setting can be provided by the
family doctor and/or domiciliary nursing staff. Palliative care
providers have particular expertise in supporting families through
this difficult time.
If symptoms such as agitation become refractory the question of
sedation for the child will arise. In this setting, the goals of
alleviating suffering and facilitating the best possible
interaction between child and family may come into conflict. For
some parents, being able to interact with their child is
fundamental to quality of life and they become understandably
concerned if this becomes impossible. In some cases however, the
adequate control of symptoms requires the use of medications and
doses which reduce the child's conscious state. Clarity around the
goals of care is vitally important in this setting as achieving
adequate symptom control may reduce the ability of the child to
interact. A crucial factor here is the family's prior experience
with the health care system. A history of open, clear communication
will facilitate appropriate management and decision making.
In the setting of severe pain, sedation does not address the
fundamental problem and should be used only in conjunction with
interventions directed specifically at alleviating pain. Morphine
and midazolam combined in a subcutaneous infusion is an effective
option in this setting.
Delirium is characterised by
- Disturbed consciousness and impaired attention
- Cognitive disturbances such as disorientation and memory
impairment
- An acute or subacute onset and fluctuation throughout the
day
Often there is a prodrome in the form of restlessness, sleep
disturbance, irritability and anxiety. Early recognition and
treatment are important.
Management includes
- Treating the underlying cause if appropriate (in many cases a
cause will not be found or death may be imminent)
eg. Medications (opioids, steroids etc)
Metabolic disturbances
Dehydration - Addressing aggravating factors
- eg. severe pain, urinary retention, hypoxia, medications,
fear
- Caring for the child in a quiet, safe environment in the
company of familiar objects (eg. a teddy) and people
- Sedating the child where necessary
Haloperidol 0.01-0.1mg/kg/dose o/iv/sc q8h
®2
and/or
*Clonazepam 0.01mg/kg sublingual q8-12h ® 2
(titrate according to response)
*Midazolam is an alternative and can be given orally, or by
continuous infusion sc or iv
Chlorpromazine is another alternative and may be given
IV/IM/o/PR
*Tolerance develops to benzodiazepines and doses may require
escalation over time.
Where the child is in the terminal phase of illness, it may not
be appropriate to seek and treat an underlying cause. Parents will
need reassurance about what is happening and guidance in terms of
how they can help their child. Even where the child seems unable to
respond, they may continue to be aware of their surroundings and so
benefit from having their parents cuddle and speak to them.
Raised Intracranial
Pressure
Corticosteroids are frequently used in the management of
vomiting and headache experienced by adult patients with raised
intracranial pressure. Caution is exercised in children however as
they appear to be more prone to the side effects of this group of
medications.
Spinal Cord Compression
Compression of the spinal cord may develop in the setting of
childhood cancer. It may occur suddenly and has the potential to
leave the patient disabled, dependent and incontinent. Early
recognition and treatment may avoid such a devastating impact on a
child's quality of life.
The development of back pain or a change in the character of
existing back pain may indicate impending spinal cord compression.
The pain tends to be sharp and more severe when lying down or
coughing. Vertebral tenderness may be found on examination at this
stage. Sensory symptoms and signs in the legs develop next followed
by motor impairment and sphincter disturbances. The outcome of
treatment will depend on the degree of neurological impairment at
the time of intervention so the child's oncologist should be
consulted as soon as cord compression is suspected.
Acknowledgements
The authors would like to acknowledge the kind assistance of Dr.
Peter McDougall, neonatologist and Dr. Lloyd Shield, neurologist in
reviewing the manuscript.
References
1 Woodruff R. Symptom control in advanced cancer (2nd Edition).
Asperula, Melbourne 2002.
2 Therapeutic Guidelines: Palliative care. Therapeutic
Guidelines. Melbourne 2000.
3 Kemp CA, McDowell JM (Eds). Paediatric Pharmacopoeia (13th
Edition). Royal Children's Hospital Melbourne 2002
4 Therapeutic Guidelines: Neurology. Therapeutic Guidelines.
Melbourne 2002.