**3. Summary**

and young people with newly abnormal cerebellar or other central neurological function'. Furthermore, referral should be for urgent specialist assessment (and not a cancer pathway) in order to circumnavigate any issues with weekend cover, differences in local service con-

The guidelines point out that trade-off between net health benefits and resource utilisation are not supported by published economic analysis. It is likely that the above recommendations will result in an increase in MRI scanning with a subsequent reduction in GP attendance, because of fast-tracking medical clearance or diagnosis. In fact, the guidelines predict that

An evidence-based clinical guideline, 'Diagnosis of Brain Tumours in Children', was developed in 2010 by Wilne et al. [105]; it was informed by a systematic literature review, metaanalysis and cohort study [36]. As a result, six main categories of symptoms were identified: headache, nausea and vomiting, visual abnormalities, motor abnormalities, growth, development and behavioural abnormalities. Within the category of behavioural symptoms, lethargy and withdrawal were important neuropsychiatric signs of childhood CNS tumours. The importance of lethargy in diagnosing paediatric CNST has been highlighted by other studies [106, 107]. In fact, the prominence of lethargy in a series of 'sudden death from obstructive hydrocephalus due to intracranial lesions' prompted the authors to conclude that persistent lethargy should be considered a neurological symptom instead of a non-

The relevance of such symptoms in childhood CNST was also highlighted by an earlier study by Wilne et al. [36], in which 'behavioural and educational' symptoms were the presenting feature of brain tumours in children in 10% of cases, and were apparent in 44% of the patients. The behavioural symptoms included: lethargy (majority), irritability, personality change, aggression and emotional lability; and the educational symptoms included deterioration in reading and writing (majority), memory difficulty, poor concentration, global deterioration

Nevertheless, lethargy remains an unspecific symptom with many faces: it is prominent among physical syndromes relating to malignancy, infection, and inflammation; it is also a core psychiatric symptom in both affective (i.e., depression) and psychotic disorders (i.e., negative syndrome of schizophrenia). Despite such diagnostic opaqueness, the guidelines produced by Wilne et al. [105]—which recommend CNS imaging if lethargy or withdrawal persists for 4 weeks or more—have demonstrated promising results in initial UK studies. These successes include a reduction in median symptom interval, time between symptom onset, and

In addition to knowledge about when to suspect a brain tumour, it is important for those practicing in primary and secondary care to be familiar with the most comprehensive and current guidelines for childhood neuropsychiatric presentation of brain tumours, as outlined

such action will actually constitute a small decrease in overall costs [101].

figuration, etc.

186 Brain Tumors - An Update

specific clinical sign [108].

and decrease in school attendance.

below [26].

ultimately, the diagnosis of brain tumours in children [105].

#### **3.1. Red flags**

Recommendations for detecting malignancy in a childhood neuropsychiatric case:

	- internalising behaviour,
	- withdrawal,
	- social problems,
	- somatic complaints,
	- externalising problems,
	- depression and/or anxiety
	- hyperactivity.
	- eating disorder and
	- first episode of psychosis.
	- atypical psychiatric symptoms,
	- unexplained behavioural and/or mood changes,
	- unexplained deteriorating school performance or developmental milestones,
	- personality change,
	- disinhibited or inappropriate behaviour,
	- pathological laughter,
	- emotional lability,

○ especially emotional reactions disproportionate to significance or severity of trigger,

○ abnormal fundoscopy

• Visual assessment including fundoscopy:

• Growth and developmental abnormalities:

○ delayed, arrested or precocious puberty.

• Persistent back pain can be a symptom of cancer.

○ visual fields in school age children and older and

• Diabetes insipidus presenting with polyuria and polydipsia.

In children aged younger than 2 years, any of the following symptoms may suggest a CNS

Neuropsychiatry: Aspects of Childhood Cranial Tumours http://dx.doi.org/10.5772/intechopen.75679 189

○ proptosis.

○ acuity,

○ eye movements, ○ pupil responses,

○ optic disc appearance.

○ growth failure and

tumour and require following:

• Immediate referral:

• Urgent referral:

○ altered behaviour,

Following the diagnosis

○ abnormal eye movements, ○ lack of visual following and ○ poor feeding/failure to thrive.

○ new-onset seizures, ○ bulging fontanelle, ○ extensor attacks and ○ persistent vomiting.

○ abnormal increase in head size,

○ arrest or regression of motor development,

○ Urgency contingent on other factors: squint.

	- new-onset seizures—including focal (with/without loss of awareness) and generalised onset
	- altered consciousness,
	- cranial nerve abnormalities,
	- regression in motor skills,
	- gait abnormalities and/or abnormal motor co-ordination,
	- focal motor weakness and
	- swallowing difficulties.
	- papilledema,
	- reduced visual acuity,
	- reduced visual fields,
	- new-onset nystagmus,
	- new-onset paralytic squint,
	- optic atrophy,

○ especially emotional reactions disproportionate to significance or severity of trigger,

• Psychiatric symptoms (including behavioural) with a headache (i.e., advised to directly enquire about presence of a headache) constitute a red flag. Persistent headache that can occur at any time of the day or night requires a neurological examination. Younger children and those with communication difficulties may not be able to report headache, thus watch for behavioural representation, e.g., pointing at, holding or

• Headache and vomiting that cause early morning waking or occur on awakening are classical signs of raised intracranial pressure and an immediate referral should be made. In cases of persistent vomiting, exclude pregnancy where appropriate. Psychiatric symptoms (including behavioural) with neurological signs warrants a neurological examination. How-

○ new-onset seizures—including focal (with/without loss of awareness) and generalised

ever, a normal neurological examination does not exclude a brain tumour.

○ gait abnormalities and/or abnormal motor co-ordination,

○ flattening or blunting of affect, ○ impairment of working memory,

○ impaired executive function and

• Neurological and motor symptoms:

○ altered consciousness,

○ cranial nerve abnormalities,

○ regression in motor skills,

○ focal motor weakness and

• Visual symptoms and signs including:

○ swallowing difficulties.

○ reduced visual acuity, ○ reduced visual fields, ○ new-onset nystagmus,

○ new-onset paralytic squint,

○ papilledema,

○ optic atrophy,

○ poor attention.

188 Brain Tumors - An Update

squeezing head.

onset

○ agrammatism and dysprosody of speech,

	- acuity,
	- eye movements,
	- pupil responses,
	- visual fields in school age children and older and
	- optic disc appearance.
	- growth failure and
	- delayed, arrested or precocious puberty.

In children aged younger than 2 years, any of the following symptoms may suggest a CNS tumour and require following:

	- new-onset seizures,
	- bulging fontanelle,
	- extensor attacks and
	- persistent vomiting.
	- abnormal increase in head size,
	- arrest or regression of motor development,
	- altered behaviour,
	- abnormal eye movements,
	- lack of visual following and
	- poor feeding/failure to thrive.
	- Urgency contingent on other factors: squint.

Following the diagnosis

	- Externalising problems are less common than internalising problems but, if missed, will have significant implications for educational abilities.

profiling will enrich the clinical pre-operative prognostication and determine treatment goals

Neuropsychiatry: Aspects of Childhood Cranial Tumours http://dx.doi.org/10.5772/intechopen.75679 191

[1] Ostrom QT, Gittleman H, Fulop J, Liu M, Blanda R, Kromer C, et al. CBTRUS statistical report: Primary brain and central nervous system tumors diagnosed in the United States in 2008-2012. Neuro-Oncology. Oxford University Press. 2015;**17**(Suppl 4):iv1-iv62. DOI:

[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2017. CA: a Cancer Journal for Clinicians.

[3] Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of Tumors of the central nervous system: A summary. Acta Neuropathologica. Springer Berlin Heidelberg.

[4] Ramkissoon SH, Bandopadhayay P, Hwang J, Ramkissoon LA, Greenwald NF, Schumacher SE, et al. Clinical targeted exome-based sequencing in combination with genome-wide copy number profiling: Precision medicine analysis of 203 pediatric brain tumors. Neuro-Oncology. Oxford University Press. 2017;**19**(7):now294. DOI: 10.1093/

[5] Komori T. The 2016 WHO classification of tumours of the central nervous system: The major points of revision. Neurologia Medico-Chirurgica (Tokyo). 2017;**57**(7):301-311. DOI:

[6] Reifenberger J, Reifenberger G, Liu L, James CD, Wechsler W, Collins VP.Molecular genetic analysis of oligodendroglial tumors shows preferential allelic deletions on 19q and 1p. The American Journal of Pathology. American Society for Investigative Pathology. 1994;

[7] Hartmann C, Meyer J, Balss J, Capper D, Mueller W, Christians A, et al. Type and frequency of IDH1 and IDH2 mutations are related to astrocytic and oligodendroglial differentiation and age: A study of 1,010 diffuse gliomas. Acta Neuropathologica. 2009;

post-operatively.

**Author details**

**References**

Alexander Hegarty1,2 and Yulia Furlong1,2\*

10.1093/neuonc/nov189

neuonc/now294

**145**(5):1175-1190

10.2176/nmc.ra.2017-0010

1 Perth Children's Hospital, Perth, WA, Australia

2017;**67**(1):7-30. DOI: 10.3322/caac.21387

2016;**131**(6):803-820. DOI: 10.1007/s00401-016-1545-1

**118**(4):469-474. DOI: 10.1007/s00401-009-0561-9

2 University of Western Australia, Crawley, WA, Australia

\*Address all correspondence to: alexander.hegarty@health.wa.gov.au

• In those for whom the symptoms represent an adjustment reaction, there is an improved outcome if a truthful, complete and consistent approach to communication is taken.

When considering posterior fossa tumour resection

• The complication of cerebellar mutism is rarely mentioned to parents during the consent for surgery of a posterior fossa tumour. It is a common syndrome and, reassuringly, to the authors' knowledge there have been no reported cases of a child with cerebellar mutism not returning to some functional speech.
