**2.8. Clinical guidelines**

with midline and vermis involvement (and not lateral involvement) and was characterised by mutism, apathy and dysphoria. These symptoms presented early post-operatively, although affective and behavioural disturbances appeared at a later stage, with all symptoms, bar depression, resolving over time. In 2010, Larysz et al. [96] looked at a group of 34 children (mean age 12.3 years) with PF tumours (14 cerebellar, 20 extracerebellar) to establish whether neuropsychological deficits related to tumour location: neoplasms in the brainstem and vermis had a better outcome than those in the cerebellum. This finding was consistent with Riva et al. [97] whose sample showed an association between non-vermal tumours with language dysfunction; in the same sample, vermal tumours were more likely to present with neurobehavioural changes (emotional lability, irritability, weepiness,

In 2013, an article published by Pastore et al. [98] compared the neuropsychological profiles and behavioural symptoms in pre-school children with brain lesions: 18 of the 55 patients were brain tumour survivors and the remainder had traumatic, vascular or infectious lesions. The brain tumour group had high levels of internalising problems (77.8%); specifically, a combination of anxiety and/or depression and/or somatic symptoms and withdrawal were present in about half of the sample. However, the group with traumatic brain injury and non-cancerous brain lesions presented with externalising behaviours and aggression. These findings are consistent with those from a study of paediatric brain tumour survivors, in which the child behaviour checklist indicated that internalising behaviours (depression/ anxiety) were the most common (48.4%) psychological disorder, while externalising behaviours were present in just 11.8%. Furthermore, those aged 7–13 were most predisposed to psychological problems, whereas social maladjustment was more frequent in those older than 13. These findings were relevant as they indicated the long-term psychosocial outcome

Campen et al. [100] found a high rate of depression and adjustment disorders (30.4%) in 56 children treated for MB, particularly if they were older and male. Importantly, the multimodal therapy in MB—which is generally a protracted process—influences the neurodevelopmental maturation that is implicated in the pathogenesis of depression. Therefore, their low mood is not just explainable as an expected psychological burden; rather, it is also engendered by neurobiological mechanisms such as a disruption of hippocampal cell formation and the saturation of the limbic system. Therefore, Campen et al. found a significant difference in age at diagnosis between those who developed depression, anxiety and adjustment disorder (median 9.5 years) and those who did not (median 5.9 years), with a median time to first psychiatric symptom of 7 months. Similarly, a study of children treated for craniopharyngioma highlighted a high rate of psychiatric morbidity in the study population; 100% of subjects experienced depression; 75% suffered poor frustration tolerance and 40% had anger dyscontrol [22]. Likewise, a case series of 20 subjects described poor neurobehavioural outcomes in post-operative paediatric craniopharyngioma: 85% of subjects had some degree of internalising (apathy, poor motivation) and externalising (irritability, hyperactivity, aggression)

impulsiveness and shyness).

184 Brain Tumors - An Update

of these individuals [99].

**2.7. Psychological and adjustment disorder**

Around 9000 new primary brain and CNS tumours (CNST) are diagnosed every year in the UK, suggesting that a GP will diagnose a case every 3–5 years. Presenting complaints range from well recognised symptoms (i.e., headaches, new-onset seizures) to the more insidious, such as personality change. A combined retrospective and prospective study of 104 consecutive paediatric patients with brain tumours found that the median time from symptom onset to diagnosis was 3 months. However, diagnosis of CNST (whether primary or secondary) can be performed with the GP retaining clinical responsibility, i.e., ordering necessary diagnostic neuro-imaging tests [101].

'NICE alert symptoms' (e.g., neurological, headache, fatigue, back pain, bruising, lymphadenopathy, lump/mass/swelling, urinary symptoms, hepatosplenomegaly) and any new pattern of recurrent attendances to the GP are ominous warning signs for childhood CNST [102]. Ansell et al. [103] advised that 'the key to identifying the one child among many who merits prompt investigation is recognition of unusual symptoms, or specific symptom patterns'; these included head tilt, odd head movements, odd posture, back or neck stiffness and unsteadiness without obvious cause [103]. In concert with clinical acumen and intuition, the GP must respect the value of a parent's instinct that their child 'is not right', regardless of a specific problem *per se* [104].

The 2015 NICE guidelines, entitled 'Suspected Cancer: Recognition and Referral', features a section on 'Brain and CNS cancer' that informs clinicians about which specific symptoms in children and adolescents require investigation and/or neuro-oncological referral. Based on these symptoms, the positive predictive values (PPV) of having CNST varied in range: from <0.013% (for vomiting or headache, with loss of appetite) to 0.15 (for vomiting, in combination with unsteadiness) for patients aged 0–14 years old; and, from 0% (for primary headache) to 0.03% (for undifferentiated headache) for patients aged 5–17 years; and from 0.0029% (for pain) to 0.0238% (for seizure) for patients aged 15–24 years [101].

Adult referral was recommended for those symptoms with a PPV of 3% or above, i.e., the advantages of a suspected CNST pathway referral outweighed any disadvantages. However, in childhood cancer, such a threshold was deemed too stringent for the following reasons: (1) the high levels of treatability of these cancers, (2) early diagnosis can reduce mortality and morbidity, and (3) the number of life-years gained.

Referral at lower levels of risk than 3% is therefore permitted in children and adolescents. Accordingly, GPs/physicians/psychiatrists 'should consider a very urgent referral (for an appointment within 48 h) for a suspected brain or central nervous system cancer in children 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 configuration, etc.

**3. Summary**

**3.1. Red flags**

ther assessment and referral.

• Common psychiatric symptoms:

○ internalising behaviour,

○ withdrawal,

○ social problems,

○ hyperactivity.

• Also watch for:

○ somatic complaints,

○ externalising problems,

• Rare psychiatric symptoms:

○ first episode of psychosis.

○ atypical psychiatric symptoms,

○ unexplained behavioural and/or mood changes,

○ disinhibited or inappropriate behaviour,

○ unexplained deteriorating school performance or developmental milestones,

○ eating disorder and

○ personality change,

○ pathological laughter,

○ emotional lability,

○ depression and/or anxiety

to present with only psychiatric symptoms.

Recommendations for detecting malignancy in a childhood neuropsychiatric case:

• Childhood cancer is rare and may present initially with symptoms and signs associated with common conditions, e.g., headache, nausea and vomiting. Repeated presentation with the same problem and with no clear diagnosis should raise the suspicion and facilitate fur-

Neuropsychiatry: Aspects of Childhood Cranial Tumours http://dx.doi.org/10.5772/intechopen.75679 187

• Psychiatric symptoms are best to be considered dynamically and in combination with other signs and symptoms that are listed here. It is very rare for a childhood cranial malignancy

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

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 nonspecific clinical sign [108].

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 and decrease in school attendance.

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

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 below [26].
